The Unusual Case of Fibroma of Tendon Sheath in a Young Girl with Turner Syndrome Undergoing Growth Hormone Treatment

Fibroma of tendon sheath (FTS) is an uncommon mass that arises from the tendon sheath of extremities. The tumor typically affects adults between ages 20 and 50 years with a predominance in males. To date, growth hormone (GH) treatment is safe for children with Turner syndrome without risk factors and is accepted worldwide. This article reports the case of a nine-year-old female patient with Turner syndrome and FTS during GH treatment. She had been treated with daily subcutaneous GH to improve growth failure with a mean dose of 0.28 mg/kg/week and the level of insulin-like growth factor-1 was within the normal range. During the follow-up period, she complained about a mass in her hand, subsequently diagnosed as FTS. This report illustrates the clinical impact of Turner syndrome and GH treatments on the occurrence of this tumor through literature reviews. Further studies are needed to highlight the association between FTS and GH treatment, especially in Turner syndrome.

Lip nodules caused by hyaluronic acid filler injection: report of three cases.

Many dermal fillers have been used for reducing facial skin lines and for providing lip augmentation, and hyaluronic acid (HA) is one of the most widely used agents. One of the main commercial forms of HA is Restylane (Q Med, Sweden) produced by microbiological engineering techniques. Although HA is non-immunogenic, hypersensitivity and Granulomatous foreign body reactions have been reported. Herein, we report three female patients (average age 56 years) who presented with firm nodular lesions of the lip and a history of injection with HA (Restylane, Q Med, Sweden). Histopathologically, all cases showed pools of amorphous hematoxyphilic material surrounded by bands of densely collagenized connective tissue with no inflammation or foreign body reaction. Histochemical stains confirmed the presence of acid mucopolysaccharides such as hyaluronic acid. We conclude HA (Restylane, Q Med, Sweden) is an inert filler that may persist at an injection site, resulting in a tumor-like nodule.

Continuous phenobarbital treatment leads to recurrent plantar fibromatosis.

Despite contrary recommendations by expert opinion and international guidelines phenobarbital remains the most widely prescribed anticonvulsant worldwide. Although associated connective tissue disorders were described in a timely way after its introduction, the association between plantar fibromatosis--also called Ledderhose syndrome--and phenobarbital seems not to be well known in general. Our case series uniquely demonstrates that continuous phenobarbital treatment leads to recurrent plantar fibromatosis and may result in long-term disability and numerous unnecessary operations. In general, the association between connective tissue disorders and phenobarbital most prominently appears in adult patients of northern European descent. However, our case series and data from the literature suggest that patient groups less susceptible to connective tissue disorders may as well develop Ledderhose syndrome or other associated syndromes as Dupuytren's contractures, frozen shoulder, Peyronie's disease or complex regional pain syndrome in the course of phenobarbital treatment.

Carcinogenicity and chronic toxicity of para-chloronitrobenzene in rats and mice by two-year feeding.

Carcinogenicity and chronic toxicity of para-chloronitrobenzene (p-CNB) were examined by feeding diets containing p-CNB to rats and mice of both sexes for two years. The dietary concentration of p-CNB was 0 (control), 40, 200, or 1000 ppm (w/w) for rats and 0, 125, 500, or 2000 ppm for mice. Survival rates of the high-dosed male rats and male mice were significantly decreased compared with those of the respective controls, and this was attributed to the increased number of cancer deaths. Therefore, the high-dose levels were considered not to exceed the maximum tolerated dose. Significant decreases in red blood cell counts and hematocrit value and an increase in mean corpuscular volume were noted in the p-CNB-fed rats and mice. Nonneoplastic splenic lesions were characterized by capsule hyperplasia, fibrosis, fatty metamorphosis, and increased extramedullary hematopoiesis in rats, and congestion, increased extramedullary hematopoiesis, hemosiderin deposition, and ossification in mice. Incidences of fibromas, fibrosarcomas, osteosarcomas, sarcomas (NOS), and hemangiosarcomas in males and fibrosarcomas in females were significantly increased in the spleen of high-dosed rats. The most frequently observed splenic tumor was fibrosarcomas, followed by fibromas. The tumor incidences were increased in a dose-related manner and were more prevalent in males than in females. The malignant tumors metastasized mainly to the liver, peritoneum, and pancreas. Adrena/medullary hyperplasia and pheochromocytomas were significantly increased in the p-CNB-fed females. No tumor was induced in any of the p-CNB-fed mice of either sex except hepatic hemangiosarcomas in the 2000 ppm-fed females. Causative factors of p-CNB-induced carcinogenicity and chronic toxicity are discussed in light of the subchronic and chronic hematotoxicity reported in our present and previous studies and in the literature.

Antenatal exposure to atenolol and retroperitoneal fibromatosis.

We present a case of retroperitoneal fibromatosis in a fetus whose mother took atenolol during pregnancy. A 25-year-old obese woman was treated for hypertension with 100 mg atenolol daily from the second month until the end of pregnancy. At 29 weeks, echography disclosed a retroperitoneal mass and at 37 weeks, a boy was delivered. A biopsy of the tumor showed a fibromatosis with medullary compression, treated by antimitotics until 3 months of age. At the age of 4, the mass had disappeared but severe scoliosis was present. This in utero exposure to atenolol drew our attention because the retroperitoneal localization of the tumor is similar to that of fibroses reported in adults after exposure to atenolol and for other reasons: transplacental carcinogenesis has been demonstrated in humans, at least for diethylstilboestrol, atenolol crosses the placental barrier, the drug was taken during nearly the whole pregnancy, and retroperitoneal fibromatosis is exceptional as a neonatal tumour.

Neoplastic response in Japanese medaka and channel catfish exposed to N-methyl-N'-nitro-N-nitrosoguanidine.

Japanese medaka (Oryzias latipes) and channel catfish (Ictalurus punctatus) were investigated for carcinogenic response following a 28-day, 3 x/wk pulse exposure to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Five-wk-old medaka were exposed at concentrations of 0, 0.5, and 1.0 mg/L, and 5-mo-old catfish at concentrations of 0, 0.1, and 0.5 mg/L. In medaka, a total of 19 tumors including 2 branchioblastomas, 6 thyroid follicular adenomas and 1 adenocarcinoma, and 11 subcutaneous fibrosarcomas were observed in 16 of 96 MNNG-exposed fish. In catfish, a total of 37 tumors including 4 squamous cell carcinomas and 16 papillomas, 3 lipomas, 1 fibroma, 1 osteosarcoma, 4 branchioblastomas, 6 thymic epithelial tumors, and 2 generalized lymphosarcomas were observed in 34 of 172 MNNG-exposed fish. The induction of neoplasms in medaka was primarily in the gill, thyroid, and subcutis of the cervical and trunk regions, whereas in catfish skin, thymus, oro-pharynx, and hemopoietic tissues were also commonly affected. In both species, the neoplastic response was considered to be related to direct exposure of the tissues to MNNG. Some of these tumors have not been reported in the literature in either natural or experimental fish. The results also suggest species-specific differences in carcinogenic response following MNNG exposure.

Human lactoferrin inhibits growth of solid tumors and development of experimental metastases in mice.

The antitumor effects of the multifunctional iron-binding glycoprotein, lactoferrin (Lf), were investigated. Lf inhibited growth in mice of transplantable solid tumors induced by v-ras transformed fibroblasts and a methylcholanthrene-induced fibrosarcoma. Lf also substantially reduced lung colonization (experimental metastasis) by B16-F10 melanoma cells in syngeneic mice. Iron-saturated and apo-Lf exhibited comparable levels of tumor inhibition and antimetastatic activity. Transferrin, a related iron-binding protein, had no effect on lung colonization. In the B16-F10 system, elimination of natural killer cell activity by pretreatment of mice with anti-asialo GM1 antibody abrogated the effects of Lf, whereas inhibition of macrophage function with silica did not. The results demonstrate a novel activity for Lf and suggest a potentially important role for this molecule in the primary defense against tumorigenesis.

Induction of mesenchymal neoplasms by DMBA implantation in deep lingual submucosa of male albino rats.

45 male albino rats were used to study the effect of deep submucosal implantation of DMBA on lingual carcinogenesis. The results showed development of different mesenchymal neoplasms (fibroma, fibrosarcoma and leiomyosarcoma). So, this method of implantation could not be used as an ideal animal model for production of single known neoplasm as had been investigated by many investigators before.

Bioassay for carcinogenicity of rotenone in female Wistar rats.

Rotenone, a pesticide extracted from the Derris root, consistently was reported by a series of investigators to have induced mammary fibroadenomas in female Wistar rats when administered ip or by gavage in a sunflower (SF) oil or SF oil:chloroform vehicle. In contrast, no less than eight bioassays done in other laboratories with rotenone or rotenone-containing powders have given consistently negative carcinogenic results when different strains or species and different modes or vehicles of administration have been used. However, these studies were not designed to address the biological reproducibility of the positive data. Thus, the present study was designed to simulate conditions of the positive studies and to investigate a possible cocarcinogenic interaction between rotenone and chloroform. Each of eight treatment groups was assigned 72 weanling female Wistar rats. Groups were (1) untreated, (2) needle puncture, (3) SF oil:10% chloroform (SF oil:chloroform), (4) 1.0 mg/kg rotenone in SF oil:chloroform, (5) 2.0 mg/kg rotenone in SF oil:chloroform, (6) SF oil, (7) 1.0 mg/kg rotenone in SF oil, and (8) 2.0 mg/kg rotenone in SF oil. Rats were injected ip 5 days a week for 8 weeks (42 injection days) and subsequently held for 16 months. The appearance of palpable tissue masses was recorded; over 50 tissues from each rat were histologically evaluated. There were no statistically significant differences in overall or individual tumor incidences among control and rotenone-treated groups. Specifically, neither incidence nor time-to-palpation of mammary fibroadenoma significantly differed among control and rotenone-treated groups, regardless of the vehicle of administration. Thus, rotenone was not carcinogenic, and rotenone and chloroform did not interact to produce a carcinogenic effect in female Wistar rats in the current study. Thus, previous reports of carcinogenic activity were not reproducible under similar experimental conditions.

Expression of the transin, c-fos, and c-jun genes in rat transplantable osteosarcomas and malignant fibrous histiocytomas.

The expression of the transin, c-fos, and c-jun genes was assessed in transplantable osteosarcomas and malignant fibrous histiocytomas, as well as in pancreatic duct adenocarcinomas and hepatocellular carcinomas of rats and hamsters. Northern blot analysis revealed that both an undifferentiated osteosarcoma of spontaneous origin (SOS) and 4-hydroxyaminoquinoline 1-oxide (4-HAQO)-induced malignant fibrous histiocytomas with metastatic potential to the lung showed remarkably increased expression of transin mRNA transcripts. This was not the case for the other tumors. Interestingly, levels of transin mRNA were lower in lung metastatic lesions than in primary subcutaneous SOS tumors. The primary SOS and MFH expressed both c-fos and c-jun genes in conjunction with the transin gene, whereas the non-transin expressers, a 4-HAQO-induced osteosarcoma (COS) and the pancreatic duct adenocarcinomas, demonstrated one or the other, but not both. These results suggest a possible involvement of transin expression in the progression of spontaneous osteosarcomas and 4-HAQO-induced malignant fibrous histiocytomas in rats. Expression of the c-fos and c-jun genes may play a regulatory role in this process.

Pathological reactions in lung, liver, thymus, and spleen of rats after subacute parenteral administration of nickel sulfate.

Male Fischer-344 rats (10 to 12 rats per group) were given 14 i.m. injection of nickel sulfate (NiSO4) over a period of 26 days in order to delineate the two-year survival, body weight curves, hematocrit responses, and histopathological reactions, including carcinogenesis. Group A (vehicle controls) received the NaCl vehicle; Groups B, C, and D received NiSO4 solution at dosages of 63, 83, or 125 mumol per kg, respectively. Rats in Group D all died during the period from 4 to 32 days after the first injection; survival of rats in Groups B and C did not differ significantly from the controls (Group A). No differences were found at any time between the mean body weights or blood hematocrits of the NiSO4-treated groups vs. the controls. In Group D, histopathological lesions of the lung, liver, thymus, and spleen were consistently observed; these lesions were most severe in rats that died during the period from 22 to 32 days after the first injection. The lungs showed proliferation of alveolar lining cells, thickening of the alveolar wall, and proteinaceous alveolar exudate. The livers showed microvesicular steatosis, and necrotic hepatocytes were scattered throughout the lobules. Degeneration of lymphocytes, with pyknosis and karyorrhexis, was observed in the thymic cortex and the white pulp of the spleen. At necropsy, no significant differences were found between the NiSO4-treated rats of Groups B and C and the controls (Group A). No sarcomas or other neoplasms occurred near the injection sites in NiSO4-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of bone fracture at the site of carcinogen exposure on nickel carcinogenesis in the soft tissue.

The influence upon nickel subsulfide (alpha-Ni3S2; Ni-SS)-induced carcinogenesis in the soft tissue of bone fracture at the site of Ni-SS exposure was studied using female Fischer rats. During the one year of the experiment, the group subjected to bone fracture exhibited the shortest tumor induction time and survival time, and a significantly higher metastatic rate. The present study may suggest a model for the metastasis of human soft tissue tumors.

Progesterone receptors in estrogen-induced fibromatosis of guinea pigs.

The presence of estrogen and progesterone receptors was investigated in estrogen-induced guinea pig fibromatosis. These lesions were composed of fibroblast-like cells embedded in abundant collagen which stained positively for desmin and vimentin suggesting muscler and fibroblast differentiation. Cytosolic progesterone receptors ranging from 13 to 2045 fmol/mg protein were present in 10/13 samples while nuclear progesterone receptors were detected in 7/10 samples with values ranging from 8 to 4639 fmol/mg DNA. The Kd of the cytosolic progesterone receptor measured by a Scatchard analysis yielded a value of 3.35 X 10(-9) M with a sedimentation coefficient of 9S as determined by a sucrose gradient. Estrogen nuclear binders were found in 9/10 samples ranging from 6 to 282 fmoles/mg DNA and cytosolic estrogen binders in 10/13 with values of 9 to 349 fmoles/mg protein. The Kd of the cytosolic estrogen binder was 22 X 10(-9) M. This binder was not detected by a commercially available monoclonal antibody. Estrogen cytosolic binders and progesterone cytosolic receptors were also detected in some samples of non tumoral fibrotic tissue. It is concluded that this experimental model is appropriate for the investigation of the effects of estrogen and progesterone on proliferative fibroblastic lesions.

Histopathology of N-methyl-N-nitrosourea-induced mesenchymal tumours of the rat urinary bladder.

The present study reports the induction, histopathology, immunocytochemistry, growth pattern and proliferative behaviour of mesenchymal tumours of the urinary bladder of rats induced by a single intravesical dose (5 mg/kg/body weight) of N-methyl-N-nitrosourea (MNU). In 14 of 283 female Wistar rats (incidence: 4.9%). 16 non-epithelial tumours had developed after an experimental period of 14 months. The most common histological type induced was of fibrohistiocytic origin (eight benign-appearing and three malignant fibrous histiocytomas). Furthermore, two pure histiocytomas (one benign and one malignant) and three capillary and cavernous haemangiomas were produced. Since no metastases occurred and no clear-cut distinction between a merely expansive and a truly invasive growth was possible, the diagnosis of malignancy was based on the degree of cellular atypia and the mitotic activity. The benign-appearing fibrous histiocytomas showed a mean mitotic index of 0.06% and the malignant fibrous histiocytomas of 0.34%. The mitotic activity of the malignant histiocytoma was threefold (0.78%) as high as in the benign-appearing histiocytoma (0.25%). There exist close morphological similarities between the induced mesenchymal tumours in the rat and those occurring in the human bladder. Although the spectrum of histological types of mesenchymal tumours seen in the rat bladder was narrower than that encountered in man, MNU seems suitable for further studying the histogenesis, histopathology and biology of experimentally induced non-epithelial bladder neoplasms to gain information for a better understanding of the pathogenesis of human disease.

Amine oxidase activities in chemically-induced mammary cancer in the rat.

The activities and distributions of monoamine oxidase (MAO) and semicarbazide-sensitive amine oxidase (SSAO) were studied in solid breast tumours induced in rat by treatment with 7,12-dimethylbenz(alpha)anthracene (DMBA). It was observed that increasing degree of malignancy was associated with an increase of MAO-A activity an decrease of MAO-B and SSAO activities. The Km values did not change significantly with malignancy but Vmax values for MAO-A increased whereas Vmax for MAO-B and SSAO diminished with malignancy. It was detected in the more malignant tumours the presence of endogenous reversible inhibitor of SSAO activity not removed by dialysis.

Cancer induction in mice by 4-hydroxybenzenediazonium sulfate of the Agaricus xanthodermus mushroom.

4-Hydroxybenzenediazonium sulfate (HBD) was administered to Swiss mice by subcutaneous injection at weekly intervals of two or 36 times at 10 or 2 micrograms per gram body weight, respectively. The HBD given 36 times induced tumors of the subcutis in 22% of females and in 22% of males. The corresponding tumor incidences in the untreated controls were 2% in females and 8% in males. Histopathologically, the neoplasms were classified as fibromas, fibrosarcomas, myxosarcomas and rhabdomyosarcomas. The HBD given two times was, however, without tumor-inducing effect. HBD is an ingredient of the Agaricus xanthodermus, a non-cultivable unedible mushroom, which is closely related to the mushroom of commerce Agaricus bisporus. HBD is now the third compound of the diazonium class to exhibit carcinogenic activity.