PD-L1 and PD-1 expression in pediatric post-transplant Burkitt lymphoma and other monomorphic post-transplant lymphoproliferative disorders.

BACKGROUND: Post-transplant lymphoproliferative disorders (PTLD) develop as a consequence of immune suppression. Programmed death protein 1 (PD-1), a regulator of host immune activation, binds to programmed death-ligand 1 (PD-L1) to suppress the T-cell immune response. PD-1/PD-L1 pathway may play a role in PTLD. The objective was to describe intratumoral expression of PD-L1 and PD-1 in pediatric monomorphic PTLD, and assess if density of these cells is associated with progression-free survival (PFS) and overall survival (OS). PROCEDURE: Clinical variables and outcome data were collected on B-cell monomorphic PTLD treated in Toronto, Canada between 2000 and 2017. Diagnostic area from tumor tissue was identified to count CD3-positive or PD-1-positive cells and CD3-negative lymphoma B cells or PD-L1-positive cells. CD3+ , PD-1+ , and PD-L1+ cell densities were compared between cases of PTLD. OS and PFS were analyzed. RESULTS: We identified 25 cases of B-cell monomorphic PTLD; majority Burkitt lymphoma (32%) and diffuse large B-cell lymphoma (56%). All cases had CD3+ cells infiltrating the tumor, and median percentage of CD3+ cells was 14% (interquartile range: 6.2%-25%). Twelve cases (48%) had PD-1+ cell infiltrating (range: 1%-83%) and 13 cases (52%) had no PD-1+ cells infiltrating. Sixteen cases (64%) had PD-L1+ cells present; however, there was no PD-L1 expression on any Burkitt lymphoma tissue. When comparing PD-1 and PD-L1 expression, there was no difference in OS or PFS. CONCLUSION: Intratumoral presence of PD-1+ and PD-L1+ cells varied in pediatric patients with monomorphic PTLD; however, no relationship to OS and PFS was identified.

A Malignant Hepatoblastoma Mimicking a Benign Mesenchymal Hamartoma: Lessons Learned.

Differentiating hepatoblastomas from other congenital benign hepatic tumors is key to surgical management. We, herein, present an unusual case of an antenatally diagnosed liver lesion assessed in the neonatal period. Because of its predominantly cystic ultrasound/MRI appearance and borderline alpha-fetoprotein serum levels the diagnosis of mesenchymal hamartoma was favored and protocol-based tumor resection was performed. Due to the intraoperative diagnosis of a fetal subtype of hepatoblastoma with positive resection margins the child had to undergo a second laparotomy. This report raises awareness to an unusual appearance of hepatoblastoma and discusses noninvasive imaging clues to consider atypical appearances of hepatoblastoma preoperatively as they can have profound implications in patient management.

Pseudodiverticulum of the Cervical Esophagus With Remnant of Branchial Tissues in a Newborn: A Case Report.

Congenital pseudodiverticula of the esophagus are very rare. This case report describes the presentation, management and histopathology of a peudodiverticulum of the cervical esophagus in a neonate. The infant presented with respiratory distress and a right neck mass that required surgical excision. Pathology revealed a pseudodiverticulum that contained ectopic thymic, thyroid, and parathyroid tissue within the wall of the lesion. The presence of ectopic tissues of branchial origin and an aberrant right subclavian artery suggest an error in branchial development and neural crest cell migration.

A Novel Secondary Neoplasm Following Allogeneic Hematopoietic Stem Cell Transplant: Mixed Donor-Recipient Primitive Mesenchymal Proliferation of the Liver.

Post-hematopoietic stem cell transplant secondary solid neoplasms are uncommon and usually host-derived. We describe a 6-year-old female who developed a mixed donor-recipient origin mesenchymal stromal tumor-like lesion in the liver following an unrelated hematopoietic stem cell transplant complicated by severe graft-versus-host disease. This lesion arose early post-transplant in association with hepatic graft-versus-host disease. At 12 years post-transplant, the neoplasm has progressively shrunken in size and the patient remains well with no neoplasm-associated sequelae. This report characterizes a novel lesion of mixed origin post-transplant and offers unique insights into the contribution of bone marrow-derived cells to extra-medullary tissues.

Utility of sonography for identifying metastatic cervical adenopathy in children with differentiated thyroid carcinoma at presentation.

BACKGROUND: No study has evaluated the diagnostic accuracy of sonography for the depiction of metastatic cervical adenopathy in children with differentiated thyroid carcinoma at presentation or determined which sonographic features are most useful. OBJECTIVE: To evaluate the diagnostic accuracy of sonography for identifying metastatic cervical adenopathy in children with differentiated thyroid carcinoma at presentation and to determine the most useful sonographic features. MATERIALS AND METHODS: We evaluated cervical lymph node sonography and histology in children with proven thyroid carcinoma in a 10-year period. We excluded children in whom a preoperative sonogram was not available and those who did not have surgical resection of lymph nodes. We used histology as the gold standard. On sonography, we analyzed the size, shape, echotexture and vascularity of the lymph nodes and correlated these findings with the histology. RESULTS: We reviewed sonograms and histology of resected lymph nodes in 52 children and adolescents with proven differentiated thyroid carcinoma (33 females; ages 5-18 years, mean 13.2 years). Metastatic cervical lymph node disease was proved on histology in 33/52 (64%) of our patients at presentation. Sonographic findings correctly predicted whether the nodes were histologically involved with metastatic disease in 42/52 (81%). Sensitivity of sonography was 79%, specificity 84%, positive predictive value (PPV) 90%, negative predictive value (NPV) 70% and accuracy 81%. A significant association was seen between round shape (P=0.0002), abnormal echotexture (P≤0.0001) and vascularity (P≤0.0001), and abnormal lymph node histology. Importantly, in 11/26 (47%) patients with sonographic and histologically proven abnormal nodes, the nodes were normal in size and shape and the presence of metastatic involvement was recognized sonographically only on the basis of abnormal echogenicity and vascularity. CONCLUSION: Sonography has a high accuracy, specificity and PPV for identifying metastatic cervical lymph node involvement in children with differentiated thyroid carcinoma at presentation. Most of the abnormal lymph nodes were round in shape and had abnormal echogenicity and vascularity. Importantly, this paper emphasizes that in children, nodes with histologically proven metastases from differentiated thyroid carcinoma can be normal in size and shape. In these patients the presence of metastatic involvement might be recognized sonographically only on the basis of abnormal echogenicity and vascularity.

Posttransplant lymphoproliferative disorder in pediatric patients: Survival rates according to primary sites of occurrence and a proposed clinical categorization.

Posttransplant lymphoproliferative disorder (PTLD) is a devastating complication of organ transplant. In a hospital-based registry, we identified biopsy-proven cases of PTLD among children during a 15-year period and reviewed trends in PTLD rates, the sites of involvement, and the associated survival rates. Cases that were included had at least 1 year of follow-up after the diagnosis of PTLD. We studied 82 patients with first-episode PTLD. Median age at diagnosis was 6.4 years (IQR 3.2-12.3 years). The most frequent PTLD sites were tonsillar/adenoidal (T/A [34%]) and gastrointestinal (32%), followed by miscellaneous (defined as less common sites including central nervous system, kidney, lung, and soft tissue [12%]), lymph node (11%), and multisite (11%). Kaplan-Meier survival curves showed that T/A PTLD was associated with decreased all-cause mortality compared with PTLD at other sites (log-rank 0.004), even after adjustment for histological subtype (P = .047). PTLD-related mortality was also decreased among T/A PTLD (log-rank 0.012) but showed a trend toward significance only after adjustment for histological subtype (P = .09). Among first episodes of PTLD, T/A PTLD was associated with a survival advantage compared with PTLD at other sites, even after adjustment for potential confounders. Based on our observations, we propose a clinical categorization of PTLD according to anatomical site of occurrence.

Epididymal melanotic neuroectodermal tumor of infancy: A rare cause of scrotal mass in an infant.

Melanotic neuroectodermal tumor of infancy (MNTI) is a rare, benign neoplasm of neural crest origin more commonly seen in the craniofacial region. We report a case of MNTI of the epididymis in a 6-month-old male child with emphasis on the sonographic appearance which has not been previously described. In this case, the mass was inseparable from the testicle and therefore the differential diagnosis considered both extratesticular and intratesticular masses. MNTI should be added to the differential diagnosis of scrotal masses, particularly if they present in a child younger than 12 months of age.

NUT midline carcinoma of the larynx: an international series and review of the literature.

AIMS: NUT midline carcinoma (NMC) is a rare undifferentiated and aggressive carcinoma that locates characteristically to the midline of the head and neck, and mediastinum. NMC is characterized by chromosomal rearrangements of the gene NUT, at 15q14. The BRD4 gene on 19q13 is the most common translocation partner forming a fusion oncogene, BRD4-NUT. By the end of 2014, the International NUT Midline Carcinoma Registry had 48 patients treated for NMC. Laryngeal NMC are exceedingly rare, and we report a case series of seven cases. METHODS AND RESULTS: We searched for cases in files of different hospitals as well as a thorough search of the English language literature. The diagnosis of NMC is made by demonstration of NUT rearrangement either by immunohistochemistry, fluorescence in-situ hybridization (FISH) or reverse transcription-polymerase chain reaction (RT-PCR). We found three previously published cases, and in this series add four cases of our own. CONCLUSIONS: NMC consists of monomorphic, often discohesive, cells with an epithelioid appearance and distinct nucleoli. The tumours typically show abrupt squamous differentiation. The mean age of the patients was 34 years, hence significantly lower than that for conventional laryngeal carcinoma. All tumours were located in the supraglottis and five patients died of the disease after 3, 7, 8, 9 and 11 months. Laryngeal NMC may be underdiagnosed, and an increased awareness among pathologists is warranted. NMC has characteristic morphological features, and positive immunostaining with the NUT antibody is diagnostic. Its aggressive behaviour demands a very intense treatment strategy and the need for its recognition is emphasized further by new promising treatment strategies.

Imaging of childhood angiomatoid fibrous histiocytoma with pathological correlation.

BACKGROUND: Angiomatoid fibrous histiocytoma is a rare soft-tissue tumor that more often affects children and young adults. There is little information available regarding the imaging appearance of angiomatoid fibrous histiocytoma in children. OBJECTIVE: To describe the ultrasonographic (US) and magnetic resonance (MR) imaging findings of angiomatoid fibrous histiocytoma in children. MATERIALS AND METHODS: A retrospective analysis was done of US and MR imaging findings in children with angiomatoid fibrous histiocytoma. Clinical findings and histopathology with molecular analysis results were also collected. RESULTS: There were 7 children with angiomatoid fibrous histiocytoma with a median age of 6 years (age range: 16 months-14 years). Patients presented clinically with a soft-tissue mass in the extremities or in the trunk. Four children had anemia, and three of them had additional systemic symptoms. Two patients had US and three had MR imaging while the remaining two had both. Lesion size ranged from 1.3 cm to 7.2 cm. In four patients, angiomatoid fibrous histiocytoma presented as a nonspecific predominantly solid mass. The other three patients had a combination of the following imaging findings: intralesional blood-filled cystic spaces with fluid-fluid levels, enhancing fibrous pseudocapsule and hemosiderin deposition. These findings correlated well with histopathology. CONCLUSION: The imaging detection of intralesional blood-filled cystic spaces with fluid-fluid levels, enhancing fibrous pseudocapsule and hemosiderin deposition in a soft-tissue tumor in a child may suggest the diagnosis of angiomatoid fibrous histiocytoma. A history of systemic symptoms and anemia in the presence of a soft-tissue mass may also be a clue for the diagnosis of angiomatoid fibrous histiocytoma.

Progressive transformation of germinal centers in children and adolescents: an intriguing cause of lymphadenopathy.

BACKGROUND: The clinical implications of a diagnosis of progressive transformation of germinal centers (PTGC) in children are not well known. METHODS: To better understand this entity, we conducted a retrospective review of all patients aged 0-18 years diagnosed with PTGC at our center between 1998 and 2010. RESULTS: Twenty-nine patients were identified. Median age at diagnosis was 11.5 years, and median duration of follow-up was 2.8 years. Thirteen patients (45%) had a single episode of PTGC with no other associated features. Five patients (17%) had recurrent PTGC. Four patients (14%) had PTGC associated with Hodgkin lymphoma (HL): one preceding, two concurrent, and one subsequently developed HL. The most commonly associated HL was nodular lymphocyte-predominant HL. Seven patients (24%) had PTGC associated with immune disorders, including lupus, Castleman disease, and probable autoimmune lymphoproliferative syndrome. Overall, 15 patients (52%) had more than one lymph node biopsy. The cumulative incidence of a second biopsy after a diagnosis of PTGC was 42.3% ± 12.2% at 4 years. PTGC was PET-avid in all four patients tested. CONCLUSIONS: PTGC is a nonspecific manifestation of a variety of associated conditions. There is a small risk of subsequent HL, and a larger risk of requiring multiple biopsies for recurrent PTGC. The presence of an immune disorder should be considered in patients who present with generalized lymphadenopathy, splenomegaly, immune cytopenias, and/or progression to HL. Routine surveillance imaging may not be required. Future research should determine the optimal surveillance strategy for patients with PTGC and the indications for repeat biopsies.

Expression and Clinical Correlation of PD-1/PD-L1 and VE1(BRAFp.V600E) in Pediatric Langerhans Cell Histiocytosis.

Background And Objectives: Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasm with a wide spectrum of clinical presentations. Programmed Cell Death-1 (PD-1) receptor and its ligand (PD-L1) are overexpressed in LCH, but their clinical significance is unknown. We performed a clinical correlation study of PD-1/PD-L1 and VE1(BRAFp.V600E) expression in 131 children with LCH. Methods: A total of 111 samples were tested for PD-1/PD-L1 and 109 for VE1(BRAFp.V600E) mutant protein by immunohistochemistry. Results: PD-1, PD-L1 and VE1(BRAFp.V600E) positivity was observed in 40.5%, 31.53% and 55%, respectively. PD-1/ PD-L1 expression showed no significant effect on the rate of disease reactivations, early response to therapy or late sequelae. The 5-year EFS was not statistically different between patients with PD-1 positive compared to those with PD-1 negative tumours (47.7% vs.58.8%, p=0.17). Similar 5-year EFS rates were also seen in those who were PD-L1 positive compared to PD-L1 negative cases (50.5% vs.55.5%, p=0.61). VE1(BRAFp.V600E) positivity was associated with a significantly higher frequency of risk-organ involvement (p=0.0053), but no significant effect on early response to therapy or rates of reactivations or late sequelae. Conclusions: Our study showed no significant correlation between VE1(BRAFp.V600E) expression, PD-1 and PD-L1 and clinical outcome in pediatric LCH.

Single nucleotide polymorphisms that increase expression of the guanosine triphosphatase RAC1 are associated with ulcerative colitis.

BACKGROUND & AIMS: RAC1 is a guanosine triphosphatase that has an evolutionarily conserved role in coordinating immune defenses, from plants to mammals. Chronic inflammatory bowel diseases are associated with dysregulation of immune defenses. We studied the role of RAC1 in inflammatory bowel diseases using human genetic and functional studies and animal models of colitis. METHODS: We used a candidate gene approach to HapMap-Tag single nucleotide polymorphisms in a discovery cohort; findings were confirmed in 2 additional cohorts. RAC1 messenger RNA expression was examined from peripheral blood cells of patients. Colitis was induced in mice with conditional disruption of Rac1 in phagocytes by administration of dextran sulfate sodium. RESULTS: We observed a genetic association between RAC1 with ulcerative colitis in a discovery cohort, 2 independent replication cohorts, and in combined analysis for the single nucleotide polymorphisms rs10951982 (P(combined UC) = 3.3 × 10(-8), odds ratio = 1.43 [95% confidence interval: 1.26-1.63]) and rs4720672 (P(combined UC) = 4.7 × 10(-6), odds ratio = 1.36 [95% confidence interval: 1.19-1.58]). Patients with inflammatory bowel disease who had the rs10951982 risk allele had increased expression of RAC1 compared to those without this allele. Conditional disruption of Rac1 in macrophage and neutrophils of mice protected against dextran sulfate sodium-induced colitis. CONCLUSIONS: Human studies and knockout mice demonstrated a role for the guanosine triphosphatase RAC1 in the development of ulcerative colitis; increased expression of RAC1 was associated with susceptibility to colitis.

Osteopontin mediates Citrobacter rodentium-induced colonic epithelial cell hyperplasia and attaching-effacing lesions.

Although osteopontin (OPN) is up-regulated in inflammatory bowel diseases, its role in disease pathogenesis remains controversial. The objective of this study was to determine the role of OPN in host responses to a non-invasive bacterial pathogen, Citrobacter rodentium, which serves as a murine infectious model of colitis. OPN gene knockout and wild-type mice were infected orogastrically with either C. rodentium or Luria-Bertani (LB) broth. Mouse-derived OPN(+/+) and OPN(-/-) fibroblasts were incubated with C. rodentium and attaching-effacing lesions were demonstrated using transmission electron microscopy and immunofluorescence. Colonic expression of OPN was increased by C. rodentium infection of wild-type mice. Furthermore, colonic epithelial cell hyperplasia, the hallmark of C. rodentium infection, was reduced in OPN(-/-) mice, and spleen enlargement by infection was absent in OPN(-/-) mice. Rectal administration of OPN to OPN(-/-) mice restored these effects. There was an 8- to 17-fold reduction in bacterial colonization in OPN(-/-) mice, compared with wild-type mice, which was accompanied by reduced attaching-effacing lesions, both in infected OPN(-/-) mice and OPN(-/-) mouse fibroblasts. Moreover, adhesion pedestals were restored in OPN(-/-) cells complemented with human OPN. Therefore, lack of OPN results in decreased pedestal formation, colonization, and colonic epithelial cell hyperplasia responses to C. rodentium infection, indicating that OPN impacts disease pathogenesis through bacterial attachment and altered host immune responses.

Patterns and Predictors of Metastatic Spread to the Neck in Pediatric Thyroid Carcinoma.

OBJECTIVE: Evaluate patterns and predictors of spread to the neck in pediatric metastatic differentiated thyroid carcinoma (DTC). METHODS: Patients <18 years old undergoing thyroidectomy by a single surgeon from January 2015 to December 2019 were included. Neck sublevels were removed separately according to AJCC boundaries. Clinical outcomes included nerve injury, hypocalcemia, hematoma, and residual tumor. RESULTS: Forty-eight children underwent thyroid surgery. Thirty (63%) were for malignancy, 27 (90%) of which were DTC. Nineteen (70%) patients with DTC underwent 24 neck dissections; 19 central plus lateral and 5 central alone. The female to male ratio increased from 1:1 to 3:1 with age. Two children with lateral neck involvement had sub-centimeter primaries. Patients requiring neck dissection were more likely to have 1) diffuse sclerosing or tall cell variant, 2) T3 or T4 disease, 3) genetic mutation, 4) lymphatic invasion, 5) extracapsular extension, 6) positive resection margin. Levels IIA (79%), III (89%), IV (84%), VI (100%) were most commonly involved. Levels IB (16%), IIB (16%), VB (16%) were also involved, often without involvement of adjacent levels. Permanent injuries included one unilateral recurrent laryngeal nerve, one mild marginal mandibular nerve and one mild accessory nerve. Hypocalcemia was highest following neck dissection for malignant disease. One patient was re-operated for a mediastinal node. Most patients with N1 disease received radioactive iodine. Most patients have no evidence or indeterminate disease on long-term follow-up. CONCLUSION: Children with lateral nodal spread from DTC should be considered for neck dissection including Levels IB, IIA, IIB, III, IV, VB, bilateral VI. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1002-E1009, 2021.

Protein-tyrosine phosphatase sigma is associated with ulcerative colitis.

Inflammatory bowel disease (IBD), a relatively common chronic debilitating intestinal illness, is composed of two broadly defined groups, Crohn's disease (CD) and ulcerative colitis (UC). Although several susceptibility genes for CD have been recently described, susceptibility genes exclusive for UC have not been forthcoming. Here, we show that receptor protein-tyrosine phosphatase sigma (PTPRS-encoding PTPsigma) knockout mice spontaneously develop mild colitis that becomes severe when challenged with two known inducers of colitis. We also demonstrate that E-cadherin and beta-catenin, two important adherens junction proteins involved in maintenance of barrier defense in the colon, act as colonic substrates for PTPsigma. Furthermore, we show that three SNPs (rs886936, rs17130, and rs8100586) that flank exon 8 in the human PTPRS gene are associated with UC. The presence of these SNPs is associated with novel splicing that removes the third immunoglobulin-like domain (exon 9) from the extracellular portion of PTPsigma, possibly altering dimerization or ligand recognition. We propose that polymorphisms in the human PTPRS gene lead to ulcerative colitis.

Hypertension in children with poorly functioning unilateral kidneys: predictors of resolution after nephrectomy.

OBJECTIVE: To identify the outcome of nephrectomy and predictors of hypertension (HTN) resolution in children with poorly functioning unilateral kidneys (differential renal function, DRF of < 15%), as concurrent HTN is often an indication for nephrectomy. PATIENTS AND METHODS: Over a 7.5-year period, a single centre retrospective analysis of 89 children with unilateral nonfunctioning/poorly functioning kidney who underwent nephrectomy was conducted. Preoperative HTN was present in 18 children (20.2%). The childrens' characteristics (age, sex, body mass index, pathology, side), cause of nonfunction, diagnostics including preoperative proteinuria (dipstick) and DRF (nuclear scan), pathological features of specimen and follow-up were recorded. RESULTS: The mean (median; range) age at nephrectomy was 6.8 (5; 0.333-14) years with a mean (median; range) follow-up of 2.4 (3; 0.083-5.5) years. The mean (median; range) DRF was 6.5 (1; 0-15)%. Twelve of 18 children (67%) resolved their HTN. Age at nephrectomy, sex, side of nonfunctioning kidney and surgical approach (78% laparoscopic nephrectomy) did not correlate with HTN resolution. Persistence of HTN seemed to correlate with residual function of more than a DRF threshold of 5% (P = 0.05), the presence of preoperative qualitative proteinuria by dipstick (P = 0.03) and inflammation on pathology. CONCLUSIONS: HTN resolved after nephrectomy for poorly functioning unilateral kidney in most of the children. Persistence of HTN is probably multifactorial. Ipsilateral residual function before nephrectomy, preoperative proteinuria and pathological features of nephrectomy specimen may serve as clinically useful markers for outcome prediction.

BK virus-associated hemorrhagic cystitis presenting as mural nodules in the urinary bladder after hematopoietic stem cell transplantation.

We report an unusual sonographic presentation of late-onset hemorrhagic cystitis caused by BK virus infection in an 8-year-old who had undergone hematopoietic stem cell transplantation for treatment of relapsed acute lymphoblastic leukemia. Sonography showed the presence of multiple bladder nodules in a background of diffuse bladder wall thickening. The dominant bladder nodule showed increase in size on serial sonograms and was vascularized on Doppler interrogation. Biopsy confirmed BK virus-associated cystitis. Recognition of this sonographic appearance in the appropriate clinical setting might obviate the need for biopsy in these children.

Identification of EpCAM as the gene for congenital tufting enteropathy.

BACKGROUND & AIMS: Congenital tufting enteropathy (CTE) is a rare autosomal recessive diarrheal disorder presenting in the neonatal period. CTE is characterized by intestinal epithelial cell dysplasia leading to severe malabsorption and significant morbidity and mortality. The pathogenesis and genetics of this disorder are not well understood. The objective of this study was to identify the gene responsible for CTE. METHODS: A family with 2 children affected with CTE was identified. The affected children are double second cousins providing significant statistical power for linkage. Using Affymetrix 50K single nucleotide polymorphism (SNP) chips, genotyping was performed on only 2 patients and 1 unaffected sibling. Direct DNA sequencing of candidate genes, reverse-transcription polymerase chain reaction, immunohistochemistry, and Western blotting were performed on specimens from patients and controls. RESULTS: SNP homozygosity mapping identified a unique 6.5-Mbp haplotype of homozygous SNPs on chromosome 2p21 where approximately 40 genes are located. Direct sequencing of genes in this region revealed homozygous G>A substitution at the donor splice site of exon 4 in epithelial cell adhesion molecule (EpCAM) of affected patients. Reverse-transcription polymerase chain reaction of duodenal tissue demonstrated a novel alternative splice form with deletion of exon 4 in affected patients. Immunohistochemistry and Western blot of patient intestinal tissue revealed decreased expression of EpCAM. Direct sequencing of EpCAM from 2 additional unrelated patients revealed novel mutations in the gene. CONCLUSIONS: Mutations in the gene for EpCAM are responsible for CTE. This information will be used to gain further insight into the molecular mechanisms of this disease.

Pediatric soft-tissue tumors and pseudotumors: MR imaging features with pathologic correlation: part 2. Tumors of fibroblastic/myofibroblastic, so-called fibrohistiocytic, muscular, lymphomatous, neurogenic, hair matrix, and uncertain origin.

In the final part of this two-part review article on soft-tissue masses in children, the magnetic resonance (MR) imaging features, clinical findings, and pathologic findings in a wide variety of tumors, including those of fibroblastic/myofibroblastic origin, so-called fibrohistiocytic tumors, smooth-muscle tumors, skeletal-muscle tumors, tumors of uncertain differentiation, and lymphoma, are described. Other neoplasms that are not included in the World Health Organization classification of soft-tissue tumors but may be seen clinically as soft-tissue masses, specifically dermatofibrosarcoma protuberans, neurogenic tumors and pilomatricoma, are also included. In contrast to the tumors reviewed in Part 1 of this review, the MR imaging features and clinical findings of the tumors included here are largely nonspecific. However, MR imaging is useful in determining site of tumor origin, extent of disease, and relation of tumor to adjacent anatomic structures, and for follow-up after therapy. In some of these entities, the combination of findings may aid in narrowing the differential diagnosis, such as persistent low signal intensity on T1- and T2-weighted images in some fibroblastic lesions, identification of hemosiderin and a synovial origin in pigmented villonodular synovitis, or the presence of multiple target signs on T2-weighted images in deep plexiform neurofibroma. In a large number of cases, however, tissue biopsy is required for final diagnosis.

Pediatric soft-tissue tumors and pseudo-tumors: MR imaging features with pathologic correlation: part 1. Imaging approach, pseudotumors, vascular lesions, and adipocytic tumors.

A wide spectrum of entities may give rise to soft-tissue masses in children, including benign and malignant tumors, pseudotumors, and both neoplastic and nonneoplastic vascular lesions. Because of its excellent tissue contrast, multiplanar capability, and lack of ionizing radiation, magnetic resonance (MR) imaging has become the modality of choice in the evaluation of deep and large soft-tissue masses in children. In the vast majority of cases, however, accurate interpretation of the MR imaging findings requires correlation with the clinical findings. For example, in most posttraumatic and inflammatory pseudotumors, the clinical history is fundamental to establishing the diagnosis. In the evaluation of periarticular cysts, the location of the mass and its relationship to a joint are crucial for diagnosis, whereas in the evaluation of vascular lesions, including hemangiomas and vascular malformations, clinical findings combined with MR imaging findings are needed for accurate diagnosis in most cases. The identification of fat within adipocytic tumors is useful, but tissue biopsy may be required for final diagnosis. Nevertheless, MR imaging is useful in determining the origin and character of pediatric soft-tissue masses, defining their extent and their relationship to adjacent structures, and performing posttherapy follow-up.