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Giant focal nodular hyperplasia (GFNH) is rarely seen in children, presenting complex diagnostic and management considerations. Pathognomonic radiographic findings can be absent in this population, and the nuances of pathologic examination are critical. We present a child with a GFNH involving the right side of the liver arising in the background of hepatic steatosis. The details of the diagnosis and therapeutic decisions involved in his treatment are discussed.

Pulmonary complications are common in children following hematopoietic cell transplantation (HCT) and contribute to their morbidity and mortality. Early diagnosis is essential for management and prevention of progression of lung injury and damage. In many cases, diagnosis can be challenging and may require diagnostic imaging and more invasive testing such as bronchoscopy and lung biopsy. We report the case of a 12-year-old girl who developed recurrent episodes of acute respiratory failure requiring intensive care unit admission in the post-HCT phase and describe the diagnostic and multidisciplinary approach for her management. In addition, we review the diagnostic approach of pulmonary complications post-HCT and highlight the utility and risks of bronchoscopy and lung biopsy in these children.

We describe the clinical, radiologic, and pathologic features of primary bone anaplastic large cell lymphoma (ALCL) in 3 boys. Radiologic imaging showed lytic lesions involving sacrum, femur, or rib. Bone was the only site of disease in 2 cases; an associated partial lymph node was involved in case 3. Differential diagnoses included osteomyelitis and small round cell tumors of childhood, particularly Ewing sarcoma. Preoperatively, ALCL was not a diagnostic consideration in any case. Two cases showed classic large pleomorphic cells; 1 showed a composite pattern with a distinct small cell component and the more typical large cell type. Neoplastic cells in all cases showed strong CD30 and anaplastic lymphoma kinase expression with relatively weak epithelial membrane antigen positivity. Cytotoxic granule protein was expressed in 2 cases. All cases showed unusually strong expression of neuron-specific enolase (NSE). Two patients were disease-free at last follow-up (15 months and 11 years); 1 patient died of disseminated disease within a year of diagnosis. ALCL should be considered a diagnostic possibility when evaluating neoplastic bone lesions in children. Although expression of NSE in ALCL has not been emphasized in the literature, it is worth noting because it may pose a diagnostic pitfall.

Synovial sarcomas are highly malignant tumors of soft tissue which are characterized by the t(X;18) resulting in SYT-SSX fusion transcript production. Diagnosis of these tumors based on histology can be challenging, particularly when minimal biopsy specimens are presented to the pathologist. Demonstration by molecular methods of SYT-SSX transcripts is a useful adjunct for diagnosis in these situations. We have developed an assay, which combines one-step RT-multiplex PCR with capillary electrophoresis to detect and genotype the SYT-SSX transcripts from synovial sarcomas. Small amplicons from chimeric transcripts as well as GAPD transcripts are differentially labeled with fluorophores, allowing detection and size discrimination by capillary electrophoresis. In a study of 32 formalin-fixed soft tissue tumor specimens, the assay detected chimeric transcripts from 17/22 (77%) synovial sarcomas. All five assay negative specimens yielded no intact RNA as evidenced by lack of a GAPD amplicon. Chimeric transcripts were not detected in 9/9 malignant peripheral nerve sheath tumors or 1/1 epithelioid sarcoma. Representative amplicons were sequenced and confirmed the genotype results obtained by capillary electrophoresis. One-step RT-multiplex PCR combined with capillary electrophoresis is a rapid and accurate method for the detection and genotypic classification of SYT-SSX transcripts from fixed tissue specimens.

Angiomyolipoma is a tumor of the kidney and, more rarely, the liver, which histologically consists of smooth muscle cells, adipose cells, and abnormal blood vessels in varying proportions. This tumor is generally benign and resection is curative, but here the authors present the case of a 14-year-old girl with an unusual primary hepatic angiomyolipoma that recurred following resection and behaved aggressively. Despite stabilization with a number of novel therapies, the child ultimately died of progressive disease.

Nonhuman primates represent phylogenetic intermediates for studying the divergence of human and murine β 2 Ms. We report the nucleotide sequences of B 2 m cDNA clones from a baboon cell line, 26CB-1 ( Papio hamadryas ); primates: Cercopithecoida), and a cotton-top tamarin cell line, 1605L ( Saguinus oedipus ; primates: Ceboidea). The baboon and tamarin B 2 m sequences indicate a very slow rate of B 2 m evolution in primates relative to that in murid rodents. Phenotypic evolution of β 2 M has also been very conservative in primates, with only 9–14 substitutions separating baboon or tamarin β 2 Ms from those of humans or orangutans. Analyses of silent and amino-acid-altering nucleotide substitutions provide evidence that negative selection has acted to limit variability in β strands of primate β 2 Ms, while positive selection has promoted diversity in non-β-strand regions of murine β 2 Ms. No evidence for the action of selection upon β 2 M residues that contact the class I heavy chain was found in primates or mice. The finding that different selective forces have operated upon primate and murine β 2 Ms suggests that β 2 M may have evolved to serve distinct functions in primates and mice.

Birth depression unresponsive to conventional resuscitative measures merits careful consideration. The case of a term infant with primary respiratory failure at birth despite extensive intervention is presented. Postmortem examination revealed bilateral pulmonary artery thrombi, which underscores the importance of careful exploration of possible pathogenetic mechanisms.

Congenital infantile fibrosarcoma is a rare soft tissue malignancy that occurs in both axial and extremity locations. We report a case of this tumor arising from the left colon in a newborn presenting with an intrauterine perforation and meconium peritonitis.

A 7-year-old boy presented with a 1-year history of back pain radiating to his left scapula and arm, with tenderness to palpation over the area. Laboratory studies were unremarkable. Computed tomographic scan showed a mixed lytic and sclerotic process at the T5-T6 level of the vertebral column in continuity with an adjacent paravertebral soft tissue mass. Nuclear medicine scan demonstrated increased uptake in the T5 vertebral body. Histology revealed invasive squamous cell carcinoma infiltrating mature, gliotic neural tissue, with areas of necrosis and prominent perivascular space involvement. Associated vertebral fragments showed bone destruction, reactive bone formation, and fibrosis. By immunohistochemistry, the carcinoma cells were positive for cytokeratin AE1/AE3, cytokeratin 5/6, EMA, and MIC-2 (membranous staining). The mature neural tissue was positive for GFAP; immature neural elements were not identified. Based on morphologic, immunohistochemical, and clinical features, this lesion was diagnosed as invasive squamous cell carcinoma arising within an intravertebral and paravertebral teratoma.

We report a 3-year-old boy with a malignant triton tumor (MTT) involving the left masticator space with local invasion and regional lymph node metastasis. Family history and detection of a novel germline TP53 mutation confirmed his diagnosis of Li Fraumeni syndrome (LFS). MTT has not been previously described in association with LFS. This case along with a comprehensive review of the literature, illustrate the importance of both somatic and germline TP53 mutations in the pathogenesis MTT. The tumor could not be resected and he was successfully treated with intensive induction chemotherapy, irradiation, and high-dose chemotherapy with autologous stem cell transplantation.

Background: Infantile myofibromatosis is the most common fibrous tumor of infancy. It can involve the skin, muscle, bone, and viscera. This uncommon entity is subdivided into solitary and multicentric forms, with or without visceral involvement. Objective: To describe the imaging characteristics of extracranial myofibromatosis. Materials and methods: Six infants, aged 1 day–1 week, were evaluated by imaging. All six patients had evaluation of one of the masses by US; four patients had CT evaluation of at least one of the masses; and five patients had evaluation by MRI. Results: The US appearance of the myofibromas included a mass with a purely anechoic center with a thick wall, a mass with a partially anechoic center, and a mass without anechoic components. On enhanced CT, the masses had lower or similar attenuation compared to adjacent muscle, with some masses exhibiting peripheral enhancement. The MR appearance consisted of low signal on T1-weighted imaging. On T2-weighted imaging, two had low signal of the center and the other three had high signal. All masses showed peripheral enhancement after gadolinium administration. Conclusions: Myofibromas have variable appearance on US, with a mass with an anechoic center being the most common feature. On CT, the mass can exhibit peripheral enhancement, calcifications, and erosion of adjacent bone. The MR appearance consisted of low signal on T1-weighted imaging and high or low signal of the center on T2-weighted imaging. All masses showed peripheral enhancement after gadolinium administration.

A 2-year-old boy with blindness as an isolated symptom was found to have no light perception binocularly because of compression of both optic nerves by a neuroblastoma infiltrating the walls of the optic canals and medial sphenoid bone. Imaging disclosed a primary tumor near the kidney and multiple osseous metastases. Although neuroblastoma commonly causes blindness by metastasis to the orbit, it rarely causes bilateral blindness from intracranial compression of the optic nerves. This is the first report of bilateral blindness as the presenting feature.

Structural characteristics of major histocompatibility complex class I antigens associated with natural killer (NK)-resistance phenomena were examined. Previous research has shown that transfection of class I genomic DNA clones into class I-deficient, NK-sensitive target cell lines results in transfectants exhibiting class I+, NK-resistant phenotypes. In contrast to the HLA-A3, -B7, -B27, and -Bw58 class I molecules, the HLA-A2 class I molecules were shown not to protect target cells from NK activity. Here we show that this nonprotective phenotype maps to the alpha 1 domain of the HLA-A2 molecule by examining the NK-protective capacity of the natural interdomain recombinant HLA-Aw69 molecule. HLA-Aw69, which consists of an alpha 1 domain exhibiting homology with HLA-Aw68, and alpha 2/alpha 3/transmembrane-cytoplasmic domains, exhibiting homologies with HLA-A2, mimics HLA-Aw68 and provides HLA-A,B null target cell (C1R) transfectants with increased resistance to NK. Further, the inability of transfected HLA-A2 to confer protection against NK activity can be completely attributed to the expression of a "nonpermissive" residue at position 74 in the alpha 1 domain. Site-directed mutation of the His-74 residue in HLA-A2 to the Asp-74 (HLA-A3, -Aw68, -Aw69, -B7) residue generates a mutant that provides C1R cell line transfectants an NK-resistant phenotype. As His-74 blocks access to a side pocket in the HLA-A2 antigen-binding cleft, these results support the critical involvement of residues within the peptide-binding groove of class I molecules in determining the NK susceptibility phenotype of class I+ target cells.

The HLA-B5,B35 cross-reacting group is a large and serologically complex antigen family which includes the World Health Organization-recognized specificities. HLA-B5,B51,Bw52,B35,B18,Bw70,Bw71, and Bw72. In addition, several variants of antigens in this cross-reacting group have been described in the past but have not yet gained official recognition. A genetic basis for the complexity and the protein and molecular bases of this highly cross-reactive and polymorphic cross-reacting group have yet to be established. The potential contributions of shared amino acid sequences, the occurrence of multiple epitopes on a single HLA-B molecule, and the presence of new HLA-C antigens have been difficult to resolve. To address this issue, we have carefully examined the serologic reactions of more than 900 allo- and monoclonal antibodies (Tenth International Workshop, Third Asia-Oceanic Workshop, and local reagents) versus lymphocytes from 92 individuals of diverse ethnic origin (North American Caucasians, North American blacks, Amerindians, Middle Eastern Caucasians), 84 of whom were informative for the HLA-B5,B35 cross-reacting group and related antigens. Our results demonstrate that the HLA-B5,B35 gene products share different combinations of distinct epitopes. We have constructed a model for the evolution of this cross-reacting group by assigning polarity to distinct diversification steps utilizing principles of maximum parsimony.