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Abdominal inflammatory myofibroblastic tumours in children.

Inflammatory myofibroblastic tumours (inflammatory pseudotumours) occurring at intra-abdominal sites in children have rarely been described. This paper reports three patients with this tumour, two of whom presented with fever, anaemia and an abdominal mass, the third with chronic duodenal obstruction. All had experienced significant weight loss. At operation, each had a large fibrous tumour (7-18 cm in diameter) originating from the transverse mesocolon, small bowel mesentery and duodenum respectively. Intraoperative frozen section histological examination in one patient was misinterpreted as a sarcoma. All the lesions were judged to have been completely excised, but one was ruptured during operation and the patient subsequently developed recurrent tumour nodules. Abdominal inflammatory myofibroblastic tumours are rare. They may be suspected before operation but their clinical, radiological and pathological features may be confused with those of malignancy. Complete excision is necessary to avoid local recurrence.

Child↗

Teflon granuloma mimicking a thyroid tumor.

An unusual case is presented of a patient who developed a "thyroid" nodule following injection of Polytef into the left posterior vocal cord for impaired phonation. Fine-needle aspiration cytology was interpreted as suspicious for malignant cells. Histological evaluation revealed a benign granulomatous lesion with numerous Teflon particles. Review of the literature relating to Teflon injections is presented.

Adult↗

Inhibition of leukotriene function can modulate particulate-induced changes in bone cell differentiation and activity.

Aseptic loosening remains the major problem facing arthroplasty longevity with particulates from component materials touted as the cause of periprosthetic osteolysis. Proposed mechanisms in aseptic bone loss include: increased resorption, increased differentiation of osteoclasts (and/or macrophages locally), and decreased osteoblastic bone formation. Leukotrienes participate in osteoclastic bone resorption. We investigated inhibiting leukotrienes synthesis, using ICI 230487, to ameliorate the effects of particulates on osteoclast pit formation and also assessed the effects of alendronate, a bisphosphonate, on pit formation. Three particulates were used: ultra high molecular weight polyethylene (UHMWPE), polymethylmethacrylate (PMMA) and hydroxyapatite (HA). Osteoclast resorption was increased with UHMWPE, PMMA, and HA particles. Interventions with alendronate and ICI 230487 reduced particulate-induced osteoclast resorption. Both ICI 230487 and alendronate reduced osteoclast numbers at higher doses. To assess the effect of particulates on osteoclast and macrophage differentiation, mouse bone marrow was cultured and stained for tartrate resistant acid phosphatase colonies (TRAP+, osteoclasts) and nonspecific esterase positive colonies (NSE+, macrophage precursors). Particulates increased both TRAP+ and NSE+ colony formation. These increases were inhibited by ICI 230487. Particulates also inhibited osteoblast function assessed by the development of mineralized nodules and alkaline phosphatase positive (AP+) colony area. ICI 230487 partly protected osteoblast function from this particulate effect. Blockade of leukotriene production may prove a useful therapeutic intervention for particulate-induced aseptic loosening by inhibiting resorptive activity, reducing the pro-inflammatory cell populations induced and recruited by these particulates, as well as ameliorating the negative effects of inflammatory mediators on osteoblast function.

Animals↗

Survival and intra-hepatic recurrences after laparoscopic radiofrequency of hepatocellular carcinoma in patients with liver cirrhosis.

BACKGROUND: The optimal treatment for hepatocellular carcinoma (HCC) is surgical resection. However, only a small percentage of patients are operative candidates. Percutaneous radiofrequency interstitial thermal ablation proved to be effective, too. Our objective was to assess a novel operative combination of laparoscopic ultrasound (LUS) with laparoscopic radiofrequency (LRF) in the treatment of HCC not amenable to liver resection. METHODS: One hundred and four patients with HCC in liver cirrhosis were submitted to laparoscopic LRF. A LRF was indicated in patients not amenable to liver resection that had at least one of the following criteria: (a) severe impairment of the coagulation tests; (b) large tumors (but <5 cm) or multiple lesions requiring repeated punctures; (c) superficial lesions adjacent to visceral structures; (d) deep-sited lesions with a very difficult or impossible percutaneous approach; (e) short-term recurrence of HCC following percutaneous loco-regional therapies. RESULTS: The LRF procedure was completed in 102 out of 104 patients (98% feasibility rate). LUS identified 26 new malignant lesions (25%) undetected by pre-operative imaging. There was no operative mortality. Seventy-six patients had no complication (73%). At 1-month computed tomography (CT) evaluation, a complete response with a 100% necrosis was achieved in 88 out of 101 patients (87%). During the follow-up (mean follow-up: 22.5 +/- 15.9 months), 55 patients (54%) developed new malignant nodules (42% of these recurrences were localized in the same segment of the HCC treated). CONCLUSIONS: LRF of HCC proved to be a safe and effective technique at least in the short and mid-term: in fact it permits to treat lesions not treatable with the per cutaneous approach, to detect 25% of new HCC nodules and it has a low morbidity rate.

Adult↗

Tracheopathia osteoplastica: a study of the minimal lesion.

We describe the pathological findings in a case of tracheopathia osteoplastica (TPO) of minimal extent. Although described clinically such minimal lesions have not been previously studied pathologically. Our observations lend strong support to the view-point that the nodules of TPO develop as ecchondroses of the tracheal cartilage rings. It is anticipated that TPO of minimal extent will be increasingly identified clinically and diagnosed on biopsy specimens.

Humans↗

Aryl sulfotransferase IV deficiency in rat liver carcinogenesis initiated with diethylnitrosamine and promoted with N-2-fluorenylacetamide or its C-9-oxidized metabolites.

Down regulation of aryl sulfotransferase IV (AST IV) in promotion/progression of liver carcinogenesis by N-2-fluorenylacetamide (2-FAA) has been established. This study examined whether the C-9 oxidized metabolites of 2-FAA, which have recently been shown to promote diethylnitrosamine (DEN)-initiated liver carcinogenesis in male Sprague-Dawley rats, effect the above change. Hence, in DEN-initiated rats, the effects of promoting regimens of 9-OH-2-FAA or 9-oxo-2-FAA, 15 oral doses at 50 and 100 mumol/kg of body weight, were compared to those of 2-FAA at 50 mumol/kg of body weight and of the vehicle on the activity of N-hydroxy(OH)-2-FAA sulfotransferase (ST), an isozyme of AST IV and AST IV expression and distribution. Relative to the vehicle, treatment with the fluorenyl compounds led to decreased levels in hepatic N-OH-2-FAA ST activity and development of hepatic nodules and tumors which had still lower levels of the ST activity than the respective remnant livers. At approximately 8 months after treatment with the C-9-oxidized compounds at doses twice that of 2-FAA, the extents of decreases in the hepatic N-OH-2-FAA ST activity and cytosolic AST IV protein in tumors were comparable to those with 2-FAA. Immunocytochemical analysis showed close association of AST IV deficiency with neoplastic liver lesions. In comparison to N-OH-2-FAA, 9-OH-2-FAA had only low and 9-oxo-2-FAA lacked sulfate acceptor activity in the presence of male rat liver cytosol or AST IV. At 3.3-fold greater concentration than N-OH-2-FAA, 9-oxo-2-FAA inhibited (27%) the sulfate acceptor activity of N-OH-2-FAA in the presence of AST IV, which suggested interference by 9-oxo-2-FAA at the active site. Although the C-9-oxidized compounds do not appear to be substrates for N-OH-2-FAA ST, their ability to cause a decrease in N-OH-2-FAA ST activity and protein similar to that of 2-FAA supports their role in hepatocarcinogenesis. Whereas 9-OH-2-FAA had a 3.9-fold greater sulfate acceptor activity in the presence of female than male rat liver cytosol and inhibited dehydroepiandrosterone ST activity of female rat liver, N-OH-2-FAA and 9-oxo-2-FAA inhibited estrone ST activity of male rat liver, suggesting that the C-9-oxidized compounds as well as N-OH-2-FAA are substrates for STs other than AST IV.

2-Acetylaminofluorene↗

Alfalfa root nodule phosphoenolpyruvate carboxylase: characterization of the cDNA and expression in effective and plant-controlled ineffective nodules.

Phosphoenolpyruvate carboxylase (PEPC) plays a key role in N2 fixation and ammonia assimilation in legume root nodules. The enzyme can comprise up to 2% of the soluble protein in root nodules. We report here the isolation and characterization of a cDNA encoding the nodule-enhanced form of PEPC. Initially, a 2945 bp partial-length cDNA was selected by screening an effective alfalfa nodule cDNA library with antibodies prepared against root nodule PEPC. The nucleotide sequence encoding the N-terminal region of the protein was obtained by primer-extension cDNA synthesis and PCR amplification. The complete amino acid sequence of alfalfa PEPC was deduced from these cDNA sequences and shown to bear striking similarity to other plant PEPCs. Southern blots of alfalfa genomic DNA indicate that nodule PEPC is a member of a small gene family. During the development of effective root nodules, nodule PEPC activity increases to a level that is 10- to 15-fold greater than that in root and leaf tissue. This increase appears to be the result of increases in amount of enzyme protein and PEPC mRNA. Ineffective nodules have substantially less PEPC mRNA, enzyme protein and activity than do effective nodules. Maximum expression of root nodule PEPC appears to be related to two signals. The first signal is associated with nodule initiation while the second signal is associated with nodule effectiveness. Regulation of root nodule PEPC activity may also involve post-translational processes affecting enzyme activity and/or degradation.

Amino Acid Sequence↗

Effect of a perfluorochemical emulsion on the development of artificial lung metastases in mice.

Intravenous infusions of perfluorochemical emulsions, combined with administration of inspired oxygen or carbogen have been found to improve tumor oxygenation and increase the response of solid tumors in animals to radiotherapy. Fluosol-DA 20 per cent, the only perfluorochemical emulsion currently approved for testing in humans in the United States, has recently entered clinical trials as an adjunct to radiotherapy in the treatment of head and neck carcinoma. The studies reported here were undertaken as part of our laboratory evaluation of the safety and clinical potential of this oxygen-transport fluid as an adjunct to cancer therapy; they asked whether single or multiple treatments with Fluosol and an oxygen-enriched atmosphere produced immunologic perturbations, pulmonary damage, or other effects which altered the development of artificial lung metastases in experimental animals. Neither single nor multiple treatments with clinically relevant regimens of Fluosol and carbogen (95 per cent O2/5 per cent CO2) had any effect on the development of lung nodules from intravenously injected EMT6 tumor cells.

Animals↗

Long term effects of a single dose of dimethylnitrosamine on the rat liver.

A single injection of DMNA induces in hepatocytes different lesions which are revealed by the mitoses following a partial hepatectomy. The inhibition of mitotic activity, the appearance of micronuclei and the development of hyperplastic nodules were investigated. The results show that the delay between the DMNA treatment and the induction of mitotic activity influences differently the evolution of these changes. The lesions reponsible for the inhibition of mitotic activity and the production of micronuclei are produced when DMNA is given before hepatectomy. They remain unchanged for a long period and are still present five weeks after the injection of the carcinogen. They have disappeared after 10 weeks. On the contrary, the lesions leading to the formation of hyperplastic nodules are at their greatest when DMNA is given at the time of the DNA synthesis following hepatectomy. The data of the present work are compared with previous results obtained by combining X irradiation and hepatectomy.

Animals↗

"Nodules" in the achiasmatic meiosis of Bithynia (Mollusca, Prosobranchia).

In spermatocytes of Bithynia leachi and B. tentaculata, synaptonemal complexes with nodules in an achiasmatic meiosis were demonstrated for the first time by means of the spreading technique. The number and position of the nodules are different in each species and are independent of the length of the chromosomes. Although no crossing over occurs in Bithynia chiasma-like terminal connections of the chromosomes are preserved in diakinesis by the presence of the nodules. --Enzymatic treatments revealed information regarding their composition of alkaline proteins, RNA and DNA. In all proteolytic digestions the nodules more of less retain their position in the central region, while they disappear immediately if SCs are exposed to DNase. On the basis of the results a model of the composition and the function of nodules can be developed considering the concept of a lampbrush-organization of the chromosomes in early meiotic prophase.

Animals↗

Application of fine-needle aspiration biopsy for the diagnosis of dysplastic and neoplastic liver cell changes induced by N-nitrosomorpholine in rats.

Male rats were treated with the hepatocarcinogen, N-nitrosomorpholine (NNM, 10 mg ad 100 ml drinking water) for 19 weeks. Repeated fine-needle aspiration biopsies of the liver were performed percutaneously. Cytomorphologic and cytochemical criteria were used for the characterization of dysplastic and carcinoma cells. The alterations seen in the smears were correlated with histopathologic findings in the punctured liver lobes. Cells showing type I dysplasia were recognized in smears obtained from day 7 on. They corresponded to the swollen, glycogen-free cells developing in zone 3 of the Rappaport acinus during the early treatment phases. In later stages type I dysplastic cells were observed in smears. This coincided with the development of neoplastic nodules seen in histopathologic preparations. Carcinoma cells were recognized first after 15 weeks. Marked gamma-glutamyl transpeptidase (gamma-GT) activity could be demonstrated cytochemically in biopsy smears and biochemically in biopsy homogenates during the early phases of NNM-treatment. Simultaneously, a rise in gamma-GT activity was also observed in the serum.

Animals↗

Arrest and extravasation of neoplastic cells. An electron microscopy study of serial sections at sequential stages.

The morphological aspects of the arrest and extravasation of malignant cells of human origin (K-562 cell line) in the lungs of athymic (nude) and asplenic-athymic (lasat) mice were studied by electron microscopy examination of serial sections. The specimens were obtained at sequential stages after the sc inoculation into newborn mice of 10(7) malignant cells. K-562 cells (10(5)) were also injected iv into control groups of nude and lasat mice to assess the influence of the route of inoculation on the in vivo behavior of K-562 cells. Our results demonstrated that K-562 cells were arrested and proliferated within the pulmonary capillaries without the participation of platelets or fibrin. The neoplastic cells extravasated by attrition and penetration of the endothelium (rather than by diapedesis) and continued to proliferate in the interstitial tissue of the lung, developing into neoplastic nodules. Following iv injection, K-562 cells induced the formation of platelet-tumor cell aggregates within the pulmonary capillaries. However, under these conditions, the neoplastic cells did not adhere to the endothelium nor did they proliferate or extravasate. These aggregates were flushed out by the circulation, restoring the permeability of the capillaries.

Animals↗

Tumoral calcinosis revisited--common and uncommon features. Report of ten cases and review.

Familial cutaneous and subcutaneous tumoral calcifications are a recognized entity of unknown pathogenesis. The course of calcinosis and various treatments are discussed and the literature concerning the aetiology is reviewed. Our ten cases provided some experience in dealing with tumoral calcinosis and demonstrated, in addition, some clinical phenomena unrecognized previously, such as involvement of the mucous membranes and an erythematous rash preceding the development of calcified nodules.

Adolescent↗

[Electron microscopic investigation on cutaneous leiomyosarcoma (author's transl)].

A 61-year old woman developed a tumourous nodule in her left leg. Fifteen years ago a similar tumour had been removed in the same localization. Histological examination performed on biopsy material showed bundles of predominantly fusiform tumour cells with nuclear pleomorphism and many mitotic figures. Electron microscopic examination confirmed the diagnosis of leiomyosarcoma by demonstration of the ultrastructural characteristics of smooth muscle cells. Cellular differentiation showed various degree ranging from smooth muscle cell type to dedifferentiated edematous tumour cells with scanty myofilaments. An important finding was the demonstration of multiple accumulated centrioles.

Cell Differentiation↗

Disseminated bilateral hyperkeratotic variant of porokeratosis Mibelli.

Clinical, histopathological, and ultrastructural features of a new clinical variant of porokeratosis Mibelli (PM) are presented. We report a solitary case of a patient, male aged 62, who developed disseminated verrucous nodules on the buttocks and the lower extremities 3 years before diagnosis. Histopathologically, all specific signs of the keratinization disorder of PM were demonstrable; in addition, however, multiple cornoid lamellae were found at the margin as well as in the center of the lesions, which only in part showed relationships to the epidermal appendages. In the papillary dermis, numerous ectatic capillaries were conspicuous. Using electron microscopy the same specific abnormalities of the keratinization process as known from classical cases of PM could be demonstrated: autophagocytic cells that revealed perinuclear edematization and vacuolization, accumulation of autophagic vacuoles and heterolysosomes, and dyskeratotic corps ronds-like cells that become transformed to fibrillar or Civatte bodies. Problems of the classification, differential diagnosis, and pathomorphogenesis are discussed.

Age Factors↗

Adenomatous hyperplasia of the liver resembling focal nodular hyperplasia in patients with chronic liver disease.

Two nodules of hepatic adenomatous hyperplasia (AH) resembling focal nodular hyperplasia were found in two patients with cirrhosis or chronic active hepatitis. Imaging techniques suggested that the nodules were hepatocellular carcinoma. Pathological examination showed that the nodules (approximately 1.0 cm in diameter) were clearly demarcated from the surrounding liver tissue, and contained foci of scar-like fibrosis in the centre of the nodules. Microscopically, they contained portal tracts and fulfilled the criteria of AH. A large number of arteries were present in the central scar-like fibrosis as well as in the parenchyma of the nodules. There were foci of mildly atypical hepatocytes in one nodule but no cellular atypia in the other. Morphometric analysis showed that the cumulative luminal area of arteries per unit area was much greater in the nodules than in the extranodular liver tissues, while the cumulative luminal area of portal veins per unit area was much less in the nodules than in the extranodular liver tissues. Although the pathogenesis is unclear, these nodules might have developed through localized vascular changes associated with chronic liver disease, may have arisen from pre-existing arterial malformation, or may represent the early stages of angiogenesis in hepatocarcinogenesis.

Adenoma↗

Medullary thyroid carcinoma and pheochromocytoma accompanied with nodular hyperplasia in multiple endocrine neoplasia type 2.

Three patients with familial multiple endocrine neoplasia type 2 underwent total adrenalectomy and subsequently near-total or total thyroidectomy. The overt pheochromocytomas were present bilaterally in two patients and unilaterally in another patient. In addition, multiple nodules measuring a few mm in diameter were demonstrated in all adrenal medullas examined. All patients exhibited bilateral medullary thyroid carcinomas which varied in size from a few minute nodules accompanied by the microscopic C-cell hyperplasia to distinct large tumors. The thyroid C-cell hyperplasia appeared to be confined to the upper and middle thirds of the lateral lobe, and micronodules of the C-cell hyperplasia enlarged to coalesce, forming one large carcinoma mass. On the other hand, nodular hyperplasia of the chromaffin cells was distributed diffusely throughout the adrenal medulla and each nodule appeared to develop individually into a large pheochromocytoma. These findings suggested that, at least in the family members at a high risk for multiple endocrine neoplasia type 2, the development of both medullary thyroid carcinoma and pheochromocytoma was always preceded by a multicentric nodular hyperplasia. On the basis of the pathogenesis of these tumors, the most rational surgical approach was presented.

Adrenal Gland Neoplasms↗

[Bullous pemphigoid manifesting as dyshidrotic eczema and prurigo nodularis].

A 63-year-old woman presented simultaneously with two rare forms of bullous pemphigoid. Initially she had a dyshidrotic palmoplantar eczema. Repeated epicutaneous patch tests ruled out a type IV allergic reaction to common allergens. Six months later the patient developed disseminated pruritic nodules. After 4.5 years she then demonstrated scattered bullae within erythematous plaques indicative of bullous pemphigoid. A skin biopsy showed linear IgG and IgM as well as C3 deposits at the dermo-epidermal junction and circulating autoantibodies against the basement membrane could be found in serum. Accordingly, the diagnosis of bullous pemphigoid was made. In retrospect, the vesicular palmoplantar eczema and pruritic nodules could be interpreted in this case as early manifestations of bullous pemphigoid. We recommend that in patients with persistent pruritic skin lesions, which are resistant to standard therapy, bullous pemphigoid should be excluded by adequate immunological examinations.

Biopsy↗