Sirolimus therapy for fibromatosis and multifocal renal cell carcinoma in a child with tuberous sclerosis complex

A male with tuberous sclerosis complex (TSC) developed a chest wall fibromatosis and bilateral multifocal renal cell carcinoma (RCC). The fibromatosis tumor was initially resected during infancy but recurred 5 years later. At that time, bilateral RCC was also detected, leading to the resection of the more extensively affected right kidney. In an attempt to avoid bilateral nephrectomies, the patient was treated with the mTOR inhibitor sirolimus. Within 6 months of therapy, the fibromatosis and remaining RCC tumors responded substantially with minimal adverse effects. Pediatr Blood Cancer 2010;54:1035–1037 © 2010 Wiley‐Liss, Inc.     

Nonsurgical management of children with recurrent or unresectable fibromatosis

At The Children's Hospital of Philadelphia, since 1971, six children 3 months to 17 years of age with fibromatosis have been treated with a combination of vincristine, actinomycin D, and cyclophosphamide (VAC). The first three patients also received radiation therapy (5,500 rads). Locally recurrent tumors developed in four of the children after previous operative removal; the other two had tumors that could not be removed initially. The tumors arose in the neck (three patients), pelvis (two patients), or foot (one patient). In the three patients treated with VAC alone, complete disappearance of tumor was confirmed at second operation in two, and greater than 75% shrinkage on CT scans occurred in the third, all at 4 to 6 months after VAC was started. In two of the three patients who received VAC plus radiation therapy, complete disappearance of tumor occurred at 13 and 16 months; the third had no response. Five of the six patients are free of recurrent fibromatosis at 1, 2, 4, and 11 years after VAC was begun; the sixth has required multiple operations during the last 6 years. We conclude that combination chemotherapy with VAC can produce regression of fibromatosis in some children with recurrent or unresectable lesions. The administration of VAC should be considered for children with fibromatosis in whom operative removal is not feasible, would prove mutilating, or is unlikely to produce long-term control of the disease.     

MRI of fibromatosis colli

Magnetic resonance imaging (MRI) appearance of fibromatosis colli has been reported in only two cases in the literature. We herein describe the MRI findings in a case of fibromatosis colli: the signal intensity of the fusiform mass on T2 weighted images was slightly less than on T1 weighted images, consistent with the presence of some fibrous tissue within the muscle mass.     

Juvenile hyaline fibromatosis: impaired collagen metabolism in human skin fibroblasts

Juvenile hyaline fibromatosis (JHF) is inherited as a fatal autosomal recessive disorder characterised by multiple tumorous mucocutaneous proliferations. In this paper a 14 month old girl with JHF is described. For this condition, a malfunction of collagen synthesis is considered as the pathogenetic cause. Recently published data have revealed an absent band for type III collagen (TIIIC) chain in western blot studies of clinically unaffected JHF skin. Therefore supernatants of skin fibroblast cell cultures, obtained from normal human skin, were analysed for type 1 collagen (TIC) and TIIIC metabolites by radioimmunoassays. Besides the typical morphological connective tissue changes in the skin lesions, TIC synthesis and degradation were found increased in JHF fibroblasts compared with control fibroblasts. In contrast, TIIIC overall metabolism was significantly reduced by 36% compared with controls.     

Juvenile hyaline fibromatosis in one Turkish child

We describe a case of juvenile hyaline fibromatosis (JHF) in a Turkish child. Only about 40 cases of juvenile hyaline fibromatosis had been reported in English literature as of March 1998, and it had not been reported in English literature from Turkey as of November 1998. Juvenile hyaline fibromatosis characterized by multiple cutaneous masses is a rare hereditary disorder. This disease is usually found in children, and a malfunction of collagen synthesis is considered as the pathogenetic cause. In the presented case, light microscopy demonstrated an abundance of a homogeneous, amorphous, eosinophilic extracellular matrix in which fibroblasts were embedded. Well-formed collagen fibers could not be demonstrated with Gieson's method or with reticulin preparation. The hayalin material periodic acid-Schiff-positive and diastase-resistant, whereas the Congo red method was negative. Immunohistochemically, the spindle-shaped cells were actin (smooth muscle) negative.     

Ultrasound and MR imaging of fibromatosis colli (sternomastoid tumor of infancy)

The sonographic and CT findings of fibromatosis colli (sternomastoid tumor of infancy) have been described, but the MRI appearance has been reported in only one case in which the mass resolved over time. This case describes the detailed MRI findings in a biopsy-proven case of fibromatosis colli; the signal intensity of the mass on T2-weighted images was slightly less than on gradient-recalled T1-weighted images, consistent with the presence of some fibrous tissue within the muscle mass. The involved portion of the muscle was better defined on MRI than sonography. MRI was helpful in demonstrating the signal characteristics of the mass; localizing the mass to within the sternocleidomastoid muscle; and demonstrating clear surrounding fascial planes with lack of associated lymphadenopathy, airway compression, vascular encasement, bone involvement or intracranial/intraspinal extension associated with other neck masses. Received: 12 August 1997 Accepted: 21 November 1997     

Juvenile hyaline fibromatosis: impaired collagen metabolism in human skin fibroblasts

Juvenile hyaline fibromatosis (JHF) is inherited as a fatal autosomal recessive disorder characterised by multiple tumorous mucocutaneous proliferations. In this paper a 14 month old girl with JHF is described. For this condition, a malfunction of collagen synthesis is considered as the pathogenetic cause. Recently published data have revealed an absent band for type III collagen (TIIIC) chain in western blot studies of clinically unaffected JHF skin. Therefore supernatants of skin fibroblast cell cultures, obtained from normal human skin, were analysed for type I collagen (TIC) and TIIIC metabolites by radioimmunoassays. Besides the typical morphological connective tissue changes in the skin lesions, TIC synthesis and degradation were found increased in JHF fibroblasts compared with control fibroblasts. In contrast, TIIIC overall metabolism was significantly reduced by 36% compared with controls.

     

Diffuse hemispheric dysembryoplastic neuroepithelial tumor: a new radiological variant associated with early-onset severe epilepsy

The authors describe the clinical and radiological features in 3 children with a diffuse hemispheric dysembryoplastic neuroepithelial tumor (DNET) presenting with severe epilepsy and a previously unreported and characteristic MR imaging appearance. The DNET is a well-recognized cause of focal epilepsy, usually with a very good response to resection. These tumors are usually intracortical, and most commonly arise in the temporal lobe or frontal lobes. Radiologically they are usually sharply demarcated, and show little contrast enhancement. Three children (2 boys and 1 girl) presented at 14, 17, and 22 months of age with epileptic seizures. The seizures were focal motor or complex focal. One patient had epileptic spasms. The response to antiepileptic drug therapy was poor. Motor and cognitive development was delayed in all patients. One patient developed a severe epileptic encephalopathy, with regression of motor and cognitive skills. Her electroencephalogram obtained at that time showed hypsarhythmia. Admission MR imaging showed a diffuse unilateral abnormality involving frontal, temporal, and parietal lobes with little or no mass effect. There was involvement of both gray and white matter, with a striking sparing of the internal capsule in spite of apparent tumor throughout the basal ganglia and thalamus. In 2 patients there was prominent expansion of cortical gyri by tumor. In 1 child the initial radiological diagnosis was a middle cerebral artery infarct. On subsequent review the radiological diagnosis was thought to be low-grade glioma in all patients. The first patient underwent 2 limited resections involving the temporal lobe. He has continued to have poorly controlled seizures and severe behavioral and cognitive problems. The other patients had subtotal resection to the level of the internal capsule. One patient is currently seizure free 24 months postsurgery, but remains cognitively impaired. The patient in Case 3 is having some seizures 3.5 years postsurgery and remains hemiplegic, but the regression has reversed and she is making steady developmental progress. The pathological specimens showed the typical features of a DNET in all cases. This striking radiological pattern has not previously been described as a feature of a DNET. Recognition of this radiological pattern in young children with epilepsy will allow early consideration for resection, which may lead to improved long-term cognitive outcome.     

侵袭性纤维瘤基因的相关性研究

侵袭性纤维瘤(Aggressive fibromatosis,AF)又称硬性纤维瘤,局部侵袭性生长,但无远处转移能力的软组织肿瘤,手术切除是主要治疗方法,复发率高.发病机制不明确,早期检测也一直无法解决.文献报道突变的p-catenin基因腺瘤肠息肉基因(APC)可以促进侵袭性纤维瘤发生,AD-AM12、FAP、WISP1和SOX11基因在侵袭性纤维瘤中选择性高表达.     

Aggressive fibromatosis in children: a changing approach

Desmoid tumor, also known as aggressive fibromatosis (AF), is a rare monoclonal, fibroblastic proliferation arising in musculoaponeurotic structures. AF is a tumor of intermediate malignancy, with a strong potential for local invasiveness and recurrence. The treatment of choice for these tumors has been changing all the time and may involve surgery, radiotherapy and/or systemic approaches. Surgery generally used to be considered the mainstay of treatment for AF, its goal preferably being a microscopically complete resection with histologically free margins. Mutilating surgery or procedures causing significant loss of function and/or chronic symptoms should be avoided. Involvement of surgical margins is probably associated with an increased risk of local recurrence. Postoperative radiotherapy could be used in cases with positive margins after surgery, or to avoid mutilating surgery in cases of inoperable or inaccessible disease. Postoperative radiotherapy has been reported to raise local disease control to a level similar to that of complete resection, but is associated with a relatively high rate of complications. Systemic treatment may be indicated in case of locally-advanced disease. Several risk factors for local recurrence have been investigated and include: young age, large size, presentation as recurrence, girdles or intra-abdominal location, involved surgical margins, and β-catenin-activating mutations. Recently collected data prompted the suggestion that these tumors warrant a wait-and-see strategy (clinical-radiological observation, without any treatment), since their natural history is often characterized by lengthy periods of stability or even regression, considering to treat only patients with progressing or symptomatic disease.     

儿童侵袭性纤维瘤的临床特征及预后分析（附27例报告）

目的　分析儿童侵袭性纤维瘤的临床特征及预后情况,以提高临床认识及诊疗水平。方法　回顾性分析2007年1月至2018年1月首都医科大学附属北京儿童医院收治的27例原发性侵袭性纤维瘤患儿临床资料,并进行随访。结果　27例患儿中,男16例、女11例,中位发病年龄65（35,96）个月,原发肿瘤部位分型中,腹壁型3例、腹内型5例、腹外型19例。术前影像学检查提示原发肿瘤最大径中位数为9.8（5.3,12.1） cm。所有患儿初诊时均接受手术治疗,10例接受化疗（甲氨喋呤+长春碱类）。27例患儿中,无病生存9例,带瘤生存15例,死亡3例。5年总体存活率85.8%,5年无事件存活率32.6%。生存分析结果显示,手术切缘阳性与肿瘤复发相关。结论　儿童侵袭性纤维瘤是一种罕见的中间性肿瘤,手术切除效果不佳者极易复发,化疗对控制肿瘤的增长有一定作用。多数患儿预后良好,但部分患儿可因肿瘤持续增长而致残甚至死亡。     

Mesenteric fibromatosis in infants. A case

The authors report on a case of mesenteric fibromatosis in a 5 month-old infant. Surgical excision was available and the clinical course was good, without recurrence after 30 months. Clinical and histological features of mesenteric desmo?d tumor in children are discussed and diagnostic difficulties are examined in depth.     

A case of head and neck kaposiform hemangioendothelioma simulating a malignancy on imaging

Kaposiform hemangioendothelioma (KH) is an endothelial-derived spindle cell neoplasm often associated with Kasabach-Merritt syndrome. Most cases arise in infancy and childhood and are soft-tissue tumors. The tumor displays an appearance between capillary hemangioma and Kaposi's sarcoma. We report a case of KH in a 1-year-old girl involving a mass that showed abnormal enhancement of soft tissue superficial to the right temporal bone with partial destruction of the temporal bone, the temporomandibular joint, mandibular condyle, and occipital bone. The physical finding of a discolored mass led clinicians to consider a hemangiomatous lesion, whereas the radiological picture suggested a more aggressive diagnosis of rhabdomyosarcoma and aggressive fibromatosis. Received: 8 March 2001/Accepted: 6 August 2001     

Aggressive intra-abdominal fibromatosis in children and response to chemotherapy

Intra-abdominal fibromatosis (IAF) is a rare benign neoplasm arising from the abdominal fibrous tissue, mostly in the mesentery. IAF is characterized by a tendency to infiltrate the surrounding vessels and vital structures and recurrence after usually incomplete surgical removal. Accordingly, IAF is associated with considerable morbidity and mortality. The authors report on a boy who presented with a large IAF at the age of 5 years. Within 6 months after initial presentation, he underwent 4 subsequent abdominal explorations for diagnosis, tumor reduction, and intestinal obstructions. IAF was confirmed by the presence of vimentin and absence of other biological cell markers. Due to accelerated tumor growth and deteriorated general condition, as a last resort, a chemotherapy trial with vincristin and methotrexate was carried out. This regimen proved to be effective in reducing the tumor burden and improving the patient's general condition. Outcome of IAF depends on early diagnosis and complete tumor resection, and, if indicated, timely employment of neo/adjuvant chemotherapy. Radiotherapy must be considered in life-threatening conditions as the last resort in a growing child [2, 3, 4].     

H3.1 K36M mutation in a congenital‐onset soft tissue neoplasm

We describe a patient who presented with a congenital soft tissue lesion initially diagnosed as infantile fibromatosis at 15 days of age. Unusually, the mass demonstrated malignant progression leading to death at 20 months of age. Biological progression to malignancy is not known to occur in fibromatosis, and fibrosarcoma is not known to progress from a benign lesion. Whole‐exome sequencing of the tumor identified a driver mutation in histone H3.1 at lysine (K)36. Our findings support the link between oncohistones and infantile soft tissue tumors and provide additional evidence for the oncogenic effects of p.K36M in H3 variants.     

Effective treatment of multifocal aggressive fibromatosis with low-dose chemotherapy

Desmoid tumor (aggressive fibromatosis), as a member of a group of borderline neoplasms, is a rare tumor of fibroblastic origin that remains difficult to treat. Treatments with surgery, radiotherapy and different medical protocols including interferon (IFN)-alpha, hormonal agents such as tamoxifen (anti-estrogen) as well as non-steroidal anti-inflammatory drugs and low-dose antineoplastic agents have been reported. In this report we describe a new patient with multifocal aggressive fibromatosis who was successfully treated with low-dose chemotherapy consisting of methotrexate and vinblastine.     

Liposomal doxorubicin: Effective treatment for pediatric desmoid fibromatosis

Efficacy of liposomal doxorubicin (LD) in treating desmoid fibromatosis (DF) in children has not been well evaluated. This retrospective case series examines five children with progressive DF, treated with LD. We report progression‐free intervals (PFIs) and radiographic as well as clinical responses for each medication received. LD was well tolerated, with an average 4.5% reduction in tumor size and median PFI of 29 months. Treatment with LD conferred the longest PFI of all medical therapies pursued. Thus, LD is an important treatment option for DF in pediatrics.     

Eosinophilic granuloma with acute epidural hematoma: a case report.

The most common symptoms of eosinophilic granuloma are local tenderness and an enlarged skull mass. The presence of epidural hematoma is a very rare symptom of eosinophilic granuloma. To our knowledge, this is only the second reported case of eosinophilic granuloma with epidural hematoma. A 2-year-old boy with a soft tumor on the occipital scalp, palpable at the age of 3 months, yet with no obvious history of trauma, was admitted due to a sudden onset of loss of consciousness. A brain computed tomography scan showed a lytic lesion on the occipital skull with a large epidural and subcutaneous hematoma, causing brain compression. He underwent an emergency craniectomy with removal of both the tumor and hematoma. The patient regained consciousness and had no residual neurological damage. Pathological reports showed abnormal proliferation of Langerhans' cells, eosinophilic cells and multinucleated cells. A whole-body bone nuclide scan revealed no other bone lesions. The patient was discharged uneventfully. The causes of hematomas are not very clear. They may be due to tumor necrosis or minor trauma. In our presented case, the cause of the epidural hematoma may have been tumor bleeding which ruptured into the epidural space. A solitary eosinophilic granuloma of the skull with acute epidural hematoma and loss of consciousness is extremely uncommon. Craniectomy with removal of the tumor and hematoma decompression may produce good results.     

Anaplastic astroblastoma presenting as massive, sudden-onset, intraparenchymal hemorrhage

Astroblastoma is a rare primary glial tumor of children and young adults, typically located in the cerebral hemispheres and presenting as a well-circumscribed, nodular, often cystic enhancing mass. The existence of astroblastoma as a distinct clinicopathologic entity has long been debated but is recognized in the 2007 WHO classification of CNS tumors. The grading of these tumors remains unsettled. Currently, no grade has been established and there are no clearly defined diagnostic criteria for low- or high-grade tumors. Astroblastomas in general are thought to have a favorable outcome with low rates of recurrence following gross total resection. We report a case of astroblastoma with 'high-grade/anaplastic' histology in a 12-year-old, previously healthy girl. The patient experienced severe, sudden-onset headache, and quickly became comatose. Head CT showed a massive intraparenchymal hemorrhage in the right frontal lobe with surrounding edema. She underwent emergent posterior frontal craniotomy for decompression and hematoma evacuation. Pathologic examination revealed a sharply demarcated hemorrhagic heterogeneous glial tumor with focal papillary architecture, densely hyalinized blood vessels, and intensely GFAP-positive perivascular cells. The tumor showed unequivocal high-grade features including an elevated proliferative index. The diagnosis of anaplastic astroblastoma was rendered. The patient expired on postoperative day 30. This case illustrates the potential poor outcome of high-grade astroblastoma and highlights the morphologic heterogeneity of this rare neoplasm.     

Mesenteric fibromatosis in childhood

A case of omento-mesenterial fibromatosis in a 6-year-old boy revealing through acute intestinal obstruction is reported. Mesenterial fibromatosis, also known as aggressive fibromatosis or desmoid tumor is generally associated with Gardner's syndrome but otherwise an extremely rare disease. Fibromatoses do not metastasize but are characterized by a high incidence of local recurrence. Primary treatment is operative. After multiple recurrence irradiation, cytostatics and antiestrogens have been used additionally to control the disease.