Solid tumors of the peritoneum, omentum, and mesentery in children: radiologic-pathologic correlation: from the radiologic pathology archives.

Intraperitoneal solid tumors are far less common in children than in adults, and the histologic spectrum of neoplasms of the peritoneum and its specialized folds in young patients differs from that in older patients. Localized masses may be caused by inflammatory myofibroblastic tumor, Castleman disease, mesenteric fibromatosis, or other mesenchymal masses. Inflammatory myofibroblastic tumor is a mesenchymal tumor of borderline biologic potential that appears as a solitary circumscribed mass, possibly with central calcification. Castleman disease is an idiopathic lymphoproliferative disorder that appears as a circumscribed, intensely enhancing mass in the mesentery. Mesenteric fibromatosis, or intra-abdominal desmoid tumor, is a benign tumor of mesenchymal origin associated with familial adenomatous polyposis. Mesenteric fibromatosis appears as a mildly enhancing, circumscribed solitary mass without metastases. Diffuse peritoneal disease may be due to desmoplastic small round cell tumor (DSRCT), non-Hodgkin lymphoma, or rhabdomyosarcoma. DSRCT is a rare member of the small round blue cell tumor family that causes diffuse peritoneal masses without a visible primary tumor. A dominant mass is typically found in the retrovesical space. Burkitt lymphoma is a pediatric tumor that manifests with extensive disease because of its short doubling time. The bowel and adjacent mesentery are commonly involved. Rhabdomyosarcoma may arise as a primary tumor of the omentum or may spread from a primary tumor in the bladder, prostate, or scrotum. Knowledge of this spectrum of disease allows the radiologist to provide an appropriate differential diagnosis and suggest proper patient management.

Helminth protection against autoimmune diabetes in nonobese diabetic mice is independent of a type 2 immune shift and requires TGF-ß.

Leading hypotheses to explain helminth-mediated protection against autoimmunity postulate that type 2 or regulatory immune responses induced by helminth infections in the host limit pathogenic Th1-driven autoimmune responses. We tested these hypotheses by investigating whether infection with the filarial nematode Litomosoides sigmodontis prevents diabetes onset in IL-4-deficient NOD mice and whether depletion or absence of regulatory T cells, IL-10, or TGF-ß alters helminth-mediated protection. In contrast to IL-4-competent NOD mice, IL-4-deficient NOD mice failed to develop a type 2 shift in either cytokine or Ab production during L. sigmodontis infection. Despite the absence of a type 2 immune shift, infection of IL-4-deficient NOD mice with L. sigmodontis prevented diabetes onset in all mice studied. Infections in immunocompetent and IL-4-deficient NOD mice were accompanied by increases in CD4(+)CD25(+)Foxp3(+) regulatory T cell frequencies and numbers, respectively, and helminth infection increased the proliferation of CD4(+)Foxp3(+) cells. However, depletion of CD25(+) cells in NOD mice or Foxp3(+) T cells from splenocytes transferred into NOD.scid mice did not decrease helminth-mediated protection against diabetes onset. Continuous depletion of the anti-inflammatory cytokine TGF-ß, but not blockade of IL-10 signaling, prevented the beneficial effect of helminth infection on diabetes. Changes in Th17 responses did not seem to play an important role in helminth-mediated protection against autoimmunity, because helminth infection was not associated with a decreased Th17 immune response. This study demonstrates that L. sigmodontis-mediated protection against diabetes in NOD mice is not dependent on the induction of a type 2 immune shift but does require TGF-ß.

Cystic lung disease in infants and children.

Cysts within the lung are one of the more common pulmonary pathological findings seen in an active pediatric surgical pathology service. Of both developmental and acquired origin, they may present as respiratory distress in infants or may be asymptomatic lesions incidentally discovered by images studies of the thoracic for "non-pulmonary" reasons. The most frequently seen developmental cysts of the lung are those of Congenital Pulmonary Airway Malformations, types 1, 2 & 4. Other congenital cystic lesions include bronchogenic cysts (usually in older patients) and some of the enteric duplication lesions that contain cysts. Acquired cystic lung lesions include acute and persistent pulmonary interstitial emphysema, postinfarction peripheral cysts, postinfectious pulmonary cysts, and the cystic form of pleuropulmonary blastoma.

From the archives of the AFIP: breast masses in children and adolescents: radiologic-pathologic correlation.

The spectrum of breast lesions in children and adolescents varies markedly from that for adults, with the former lesions being overwhelmingly benign. A breast mass in a young boy or girl may arise from normal and abnormal breast development. Other causes of masses include infection, trauma, and cyst formation. After onset of puberty, most cases of breast enlargement arise from benign fibroadenoma in girls and gynecomastia in boys. These conditions have specific imaging appearances, although juvenile (often giant) fibroadenoma cannot be distinguished from phyllodes tumor, which can be benign or malignant. In children, both conditions usually appear as well-circumscribed, hypoechoic masses at sonography and show diffuse enhancement except for nonenhancing septations at magnetic resonance imaging. A diagnosis of juvenile papillomatosis (a benign lesion) portends later development of breast cancer, and patients with this condition should be closely monitored. Malignant lesions of the breast in children are rare. The most common malignant lesions are metastases and are usually associated with widespread disease. The most common primary breast malignancy is malignant phyllodes tumor. Primary breast carcinoma is exceedingly rare in the pediatric age group, but its imaging appearance in children is the same as seen in adults and is different from that of almost all benign lesions. In girls, diagnostic interventions may injure the developing breast and cause subsequent disfigurement. Given this risk and the low prevalence of malignant disease in this population, a prudent course should be followed in the diagnosis of breast lesions. Imaging findings are very helpful for selecting patients for further diagnostic procedures. Although malignancy is rare, lesions with suspicious imaging findings or progressive growth should be subjected to cytologic or histologic examination.

Inhibition of type 1 diabetes in filaria-infected non-obese diabetic mice is associated with a T helper type 2 shift and induction of FoxP3+ regulatory T cells.

We sought to determine whether Litomosoides sigmodontis, a filarial infection of rodents, protects against type 1 diabetes in non-obese diabetic (NOD) mice. Six-week-old NOD mice were sham-infected or infected with either L3 larvae, adult male worms, or adult female worms. Whereas 82% of uninfected NOD mice developed diabetes by 25 weeks of age, no L. sigmodontis-infected mice developed disease. Although all mice had evidence of ongoing islet cell inflammation by histology, L. sigmodontis-infected mice had greater numbers of total islets and non-infiltrated islets than control mice. Protection against diabetes was associated with a T helper type 2 (Th2) shift, as interleukin-4 (IL-4) and IL-5 release from alpha-CD3/alpha-CD28-stimulated splenocytes was greater in L. sigmodontis-infected mice than in uninfected mice. Increased circulating levels of insulin-specific immunoglobulin G1, showed that this Th2 shift occurs in response to one of the main autoantigens in diabetes. Multicolour flow cytometry studies demonstrated that protection against diabetes in L. sigmodontis-infected NOD mice was associated with significantly increased numbers of splenic CD4(+) CD25(+) FoxP3(+) regulatory T cells. Interestingly, injection of crude worm antigen into NOD mice also resulted in protection against type 1 diabetes, though to a lesser degree than infection with live L. sigmodontis worms. In conclusion, these studies demonstrate that filarial worms can protect against the onset of type 1 diabetes in NOD mice. This protection is associated with a Th2 shift, as demonstrated by cytokine and antibody production, and with an increase in CD4(+) CD25(+) FoxP3(+) regulatory T cells.

Clinical and pathologic differential diagnosis of selected potential bioterrorism agents of interest to pediatric health care providers.

The early recognition of potential bioterrorism agents has been of increasing concern in recent years. The Centers for Disease Control and Prevention has categorized and listed biological terrorism agents. Although any or all of the highest risk biological agents (including inhalation anthrax, pneumonic plague, smallpox, tularemia, botulism, and viral hemorrhagic fevers) can be seen in the pediatric patient, several agents might closely resemble--at least in their initial stages-some of the more common childhood illnesses. The awareness of these similarities and, more importantly,their differences, are critical for all health care professionals. Selected examples of some typical childhood illnesses are presented and then compared with three of the most virulent biological agents (smallpox, anthrax and plague) that might be used in a bioterrorism attack.

From the archives of the AFIP: Lung disease in premature neonates: radiologic-pathologic correlation.

Pulmonary disease is the most important cause of morbidity in preterm neonates, whose lungs are often physiologically and morphologically immature. Surfactant deficiency in immature lungs triggers a cascade of alveolar instability and collapse, capillary leak edema, and hyaline membrane formation. The term respiratory distress syndrome (RDS) has come to represent the clinical expression of surfactant deficiency and its nonspecific histologic counterpart, hyaline membrane disease. Historically, chest radiographs of infants with RDS predictably demonstrated decreased pulmonary expansion, symmetric generalized reticulogranular lung opacities, and air bronchograms. Refinements in perinatal medicine, including antenatal glucocorticoid administration, surfactant replacement therapy, and increasingly sophisticated ventilatory strategies have decreased the prevalence of RDS and air leak, altered familiar radiographic features, and lowered the threshold of potential viability to a gestational age of approximately 23 weeks. Alveolar paucity and pulmonary interstitial thickness in these profoundly premature neonates impair normal gas exchange and may necessitate prolonged mechanical ventilation, increasing the risk of lung injury. Bronchopulmonary dysplasia (BPD), alternatively termed chronic lung disease of infancy, is a disorder of lung injury and repair originally ascribed to positive-pressure mechanical ventilation and oxygen toxicity. Before the advent of surfactant replacement therapy, chest radiographs of infants with classic BPD demonstrated coarse reticular lung opacities, cystic lucencies, and markedly disordered lung aeration that reflected alternating regions of alveolar septal fibrosis and hyperinflated normal lung parenchyma. In the current era of surfactant replacement, BPD is increasingly a disorder of very low-birth-weight neonates with arrested alveolar and pulmonary vascular development, minimal alveolar septal fibrosis and inflammation, and more subtle radiographic abnormalities.

The morphologic spectrum of infantile lobar emphysema: a study of 33 cases.

Infantile lobar emphysema (ILE) is a relatively uncommon entity characterised by radiologic pulmonary lobar overinflation. The spectrum of underlying pathology in ILE has not been previously detailed. We have reviewed thirty-three cases of ILE accessioned to the Armed Forces Institute of Pathology, Washington D.C., since 1970. Seventeen (51.5%) presented in the first week of life, 27 (81.8%) presented within the first six months, and an additional six cases presented beyond six months including three beyond 18 months of age. Upper lobe involvement occurred in 96.9% cases and multiple lobes were involved in six cases. Nine infants had polyalveolar (hyperplastic) lobes determined on the basis of radial alveolar counts (RACs), while 21 were considered to be "classic ILE" since these showed lobar hyperexpansion without any other abnormality. RACs in infants with classic ILE remained fairly constant irrespective of age unlike a progressive increase seen in normal age-matched controls, suggesting a post-partum arrest of acinar development in ILE. Additional findings included serpiginous bronchioles resembling those seen in extralobar sequestration in two cases, bronchopulmonary dysplasia in two cases, and one case each showing "cystic alveoli" and peripheral subpleural cysts. ILE thus seems to be a composite of various pathologies resulting in a single clinical entity. We hypothesise that the timing of an inciting functional or anatomic bronchial obstruction during in-utero lung development determines morphologic variation in ILE.

Congenital pulmonary airway malformation (congenital cystic adenomatoid malformation) with multiple extrapulmonary anomalies: autopsy report of a fetus at 19 weeks of gestation.

Congenital pulmonary airway malformation, or congenital cystic adenomatoid malformation, is postulated to be a disorder of pulmonary airway morphogenesis and encompasses 5 different types with distinct levels or stages of tracheobronchial development. We present a unique case of type 2 congenital pulmonary airway malformation with a previously undocumented combination of multiple extrapulmonary anomalies, featuring ipsilateral multicystic renal dysgenesis, contralateral renal agenesis, and ovarian germ cell hypoplasia, diagnosed in a 19-week gestational age fetus by autopsy. Epithelial cells comprising the pulmonary lesions were positive for thyroid transcription factor-1, surfactant protein-B, and cytokeratin-7 but negative for cytokeratin-20 immunostainings, with the pattern seen in normal terminal bronchioles. Chromosomal analysis showed a normal female karyotype, despite a high estimated risk for Down syndrome suggested by the low maternal serum alpha-fetoprotein level.