Pediatric Soft Tissue Tumors Research Articles

A 5-year-old girl with a congenital ganglioneuroma diagnosed by fine needle aspiration biopsy: a case report.

IntroductionGanglioneuroma is a rare, benign, neuroblastic tumor arising mainly from the central or peripheral autonomic nervous system, especially the sympathetic system. The most affected anatomical sites are the posterior mediastinum, retroperitoneum, adrenal gland and head and neck soft tissue. In the current literature, reports of ganglioneuroma diagnosed by fine-needle aspiration and its cytological appearance are scarce.Case PresentationA 5-year-old girl presented with a mass in the cervical region since birth. Laboratory routine tests were within normal limits, ultrasonography demonstrated a solid and well-circumscribed lesion in the soft tissues of the cervical region. Fine needle aspiration biopsy was carried out, and the obtained smears showed a mixture of mature ganglion cells and groups of spindle cells suggestive of schwann cell origin. A diagnosis of ganglioneuroma was suggested. Core biopsy and surgical resection confirmed this diagnosis.ConclusionCongenital ganglioneuroma of the cervical region is an uncommon soft tissue benign neoplasm of neuroblastic origin, and it should be considered in the differential diagnosis of head and neck pediatric soft tissue tumors. Fine needle aspiration biopsy technique is a reliable method that can be used with confidence when dealing with pediatric soft tissue tumors.

Lipofibromatosis: report of a rare paediatric soft tissue tumour

The clinical, radiological and pathological features of a case of lipofibromatosis, a rare paediatric soft tissue neoplasm, are described. The tumour involved the foot of a male infant and was present at birth. Magnetic resonance imaging showed a lipomatous mass, with splaying of muscles of the sole by lobules of fat. Histopathological examination revealed typical findings of an admixture of mature adipose tissue and fibroblastic elements. The radiological and pathological features helpful in differentiating this entity from other fibro-fatty paediatric soft tissue tumours is discussed, and the relevant literature is briefly reviewed.

A multiplex assay for detection of common pediatric sarcoma tumor markers

10041 Background: Molecular assays for tumor markers have become an important component in diagnosing pediatric sarcomas and small round cell tumors. We developed a multiplex assay to detect 7 common translocations associated with synovial sarcoma (SYT/SSX1, SYT/SSX2), Ewing's sarcoma (EWS/FLI1, EWS/ERG), rhabdomyosarcoma (PAX3/FKHR, PAX7/FKHR), and small round cell desmoplastic tumors (SRCDT) (EWS/WT1). Methods: 27 samples were analyzed with the multiplex assay: 13 formalin-fixed paraffin-embedded tumor samples, 5 fresh frozen tumor samples, 2 commercial RNA samples (SYT/SSX1, SYT/SSX2), 3 cell line samples (EWS/FLI, EWS/ERG, PAX3/FKHR), 1 synthetic control (PAX7/FKHR), and 3 negative controls. After RNA extraction, RT-PCR was performed using the SuperScript III One-Step RT-PCR System with Platinum Taq DNA Polymerase (Invitrogen, Carlsbad, CA). 12 primers were added to a single master mix to amplify all 7 translocations and an internal control; 1 primer from each pair was fluorescently labeled. After RT-PCR, the PCR products were separated on a genetic analyzer and the translocations identified based on the size of the PCR products and their signal intensity. Samples were also analyzed by our current assay (real-time RT-PCR or standard RT-PCR/gel electrophoresis). Results: The results of our current and multiplex assays were positive for all synthetic controls, cell lines, and commercial RNA samples and were concordant for 15/18 tumor samples: 2/7 synovial sarcoma samples were positive for SYT/SSX1 and 3/7 for SYT/SSX2; 2/6 Ewing's sarcoma samples were EWS/FLI1-positive; 1/1 SRCDT sample was EWS/WT1-positive; and 4/4 rhabdomyosarcoma samples were negative. The 3 discordant samples tested negative with our current assay; the new multiplex assay detected EWS/FLI1 in 1 of these and SYT/SSX2 in 2, in agreement with the histological classification. Conclusions: This multiplex assay can detect 7 translocations commonly found in pediatric soft tissue tumors in a single-tube reaction, with increased clinical sensitivity relative to our current methods. No significant financial relationships to disclose.

Treatment Effects in Pediatric Soft Tissue and Bone Tumors

Dramatic improvements in survival for children with cancer have led to increased numbers of posttreatment pathologic specimens, particularly in bone and soft tissue sarcomas. Current therapeutic protocols in North America require specific pathologic classification and stratify patients based on clinical, biologic, and pathologic features. For osteosarcoma, the pathologic response to therapy predicts prognosis and modifies the treatment regimen. Ongoing studies aim to assess the response to therapy and outcome in other types of soft tissue and bone tumors. The pathologic evaluation of pretreatment and posttreatment specimens is critical for therapeutic decisions and prognostic assessment. A standardized approach to posttherapy pathologic specimens, with attention to appropriate use of ancillary tests, and assessment of clinical and biologic significance of therapy-induced pathologic changes has significance for patient management and treatment protocols.

Treatment Effects in Pediatric Soft Tissue and Bone Tumors

Dramatic improvements in survival for children with cancer have led to increased numbers of posttreatment pathologic specimens, particularly in bone and soft tissue sarcomas. Current therapeutic protocols in North America require specific pathologic classification and stratify patients based on clinical, biologic, and pathologic features. For osteosarcoma, the pathologic response to therapy predicts prognosis and modifies the treatment regimen. Ongoing studies aim to assess the response to therapy and outcome in other types of soft tissue and bone tumors. The pathologic evaluation of pretreatment and posttreatment specimens is critical for therapeutic decisions and prognostic assessment. A standardized approach to posttherapy pathologic specimens, with attention to appropriate use of ancillary tests, and assessment of clinical and biologic significance of therapy-induced pathologic changes has significance for patient management and treatment protocols.

Immunohistochemical analysis of hSNF5/INI1 distinguishes renal and extra-renal malignant rhabdoid tumors from other pediatric soft tissue tumors.

Malignant rhabdoid tumor (MRT) is a highly aggressive neoplasm that occasionally demonstrates phenotypic overlap with other soft tissue malignancies. Molecular genetic analysis of MRT frequently demonstrates deletion or mutation of the hSNF5/INI1 gene, with corresponding reduced expression at the protein level. INI1 immunohistochemistry was performed to determine the utility of this method in assessing loss of INI1 expression in rhabdoid tumors. Twenty-seven MRTs with molecular analysis (19 renal, 8 extra-renal) were evaluated. Seventeen additional MRT (10 renal, 7 extra-renal) without INI1 molecular analysis were also analyzed. Loss of INI1 expression was observed in the tumor cells in all 44 cases. To determine the specificity of this assay, a variety of 45 pediatric soft tissue tumors, some of which occasionally display rhabdoid differentiation, were investigated. These included Ewing's sarcoma, Wilms' tumor, desmoplastic small round cell tumor, clear cell sarcoma, congenital mesoblastic nephroma, synovial sarcoma, undifferentiated sarcoma, rhabdomyosarcoma, and epithelioid sarcoma. Positive nuclear staining was found in all nonrhabdoid tumors examined. Of interest, synovial and epithelioid sarcomas exhibited variable and/or focal staining. INI1 antibody immunohistochemistry is useful in confirming the histologic diagnosis of renal or extra-renal rhabdoid tumor, especially for cases with indeterminate histologic features, equivocal immunophenotypic profiles, or uninformative molecular studies.

Lipofibromatosis presenting as a pediatric neck mass

Lipofibromatosis is a recently described, benign neoplasm that presents in the pediatric population [J.F. Fetsch, M. Miettinen, W.B. Laskin, M. Michal, F.M. Enzinger, A clinicopathologic study of 45 pediatric soft tissue tumors with an admixture of adipose tissue and fibroblastic elements, and a proposal for classification as lipofibromatosis, Am. J. Surg. Pathol. 24 (2000) 1491-1500]. It is a rare soft tissue tumor histologically distinct from other fibromatoses such as juvenile fibromatosis, fibrous hamartoma of infancy, calcifying aponeurotic fibroma, and lipoblastoma. Distinguishing histopathologic features of lipofibromatosis include abundant and disorganized adipose lobules traversed by bundles of spindled fibroblast-like cells. It most commonly presents in the extremities. We present a case involving a young girl, which we believe represents the first report of lipofibromatosis involving the neck.

Ossifying fibromyxoid tumor of the ethmoid sinus in a newborn: report of a case and literature review

Ossifying fibromyxoid tumor (OFT) of soft parts is a benign soft tissue tumor commonly located in the extremities. In this paper, a 3-week-old boy presented with left nasal mass at birth. He was found to have an OFT involving the ethmoid sinus. To the best of our knowledge, this is the first reported case of OFT in a newborn with involvement of the sinuses. This rare tumor should alert Pediatric Otolaryngologists to include it in the differential diagnosis of pediatric soft tissue tumors in sinuses.

Risk assignment in pediatric soft-tissue sarcomas: an evolving molecular classification.

Pediatric soft-tissue sarcomas are increasingly being defined by both histologic appearance and underlying chromosomal abnormalities to determine their biologic behavior. Most sarcomas of this type have specific chromosomal translocations that create unique fusion genes. Expression of such fusion genes may have diagnostic, prognostic, and surveillance implications for the patient. This review analyzes the fusion gene expressions seen with seven of the major types of pediatric soft-tissue tumors and their impact on biologic behavior. In nearly 50% of the malignancies discussed, the diagnostic, prognostic, and surveillance implications of their specific fusion gene expressions are already defined or becoming established (alveolar rhabdomyosarcoma, Ewing sarcoma/primitive neuroectodermal tumor, and synovial sarcoma). In the remainder of the tumors, these questions are rapidly being addressed. To facilitate future fusion gene studies, pediatric surgeons, pathologists, and oncologists need to work as a coordinated team to ensure proper tumor procurement. Large clinical cooperative trials involving biologic studies of pediatric soft-tissue sarcomas could facilitate advancement of knowledge in this area of pediatric oncology.

Neurothekeoma of the paranasal sinuses in a 3-year-old boy

Neurothekeoma is a benign soft tissue tumor commonly located on the skin. In this report, a 3-year-old boy presented with restricted right eye movement and decrease in visual acuity. The patient was found to have a 6-cm neurothekeoma involving the maxillary and ethmoid sinuses. To our knowledge, this is the first reported case of neurothekeoma with involvement of the maxillary and ethmoid sinuses. This uncommon lesion should be considered as the differential diagnosis of pediatric soft tissue tumors in the head and neck region.

A clinicopathologic study of 45 pediatric soft tissue tumors with an admixture of adipose tissue and fibroblastic elements, and a proposal for classification as lipofibromatosis.

The tumor described here as lipofibromatosis is a rare pediatric neoplasm that has been variously interpreted as a type of infantile or juvenile fibromatosis, a variant of fibrous hamartoma of infancy, and a fibrosing lipoblastoma. This report details the clinicopathologic features associated with 45 cases of this soft tissue entity. The study group consisted of 32 males, 12 females, and one person of unstated gender. The patients presented with a soft tissue mass (range, 1-7 cm) involving the hand (n = 18), arm (n = 8), leg (n = 7), foot (n = 6), trunk (n = 5), or head (n = 1). Eight tumors were evident at birth. The individuals ranged in age from 11 days to 12 years (median age, 1 yr) at the time of initial biopsy or resection. Microscopic examination revealed abundant adipose tissue with a spindled fibroblastic element that chiefly involved the septa of fat and skeletal muscle. The process generally did not cause extensive architectural effacement of fat as is common with conventional fibromatoses, and it did not have a primitive nodular fibromyxoid component as is characteristic of fibrous hamartoma of infancy. The fibroblastic element exhibited focal fascicular growth and typically had limited mitotic activity (< or = 1 mitosis/ 10 high-power fields) and cytologic atypia. Oftentimes, small collections of univacuolated cells were present at the interface between some of the fibroblastic fascicles and the mature adipocytes. The tumors entrapped vessels (n = 45), nerves (n = 44), skin adnexa (n = 16), and skeletal muscle (n = 18). Focal immunoreactivity was present in some tumors for CD99, CD34, alpha-smooth muscle actin, BCL-2, and less frequently, S-100 protein, muscle actin (HUC 1-1), and EMA. However, no reactivity was detected for desmin (D33 and D-ER- 1 clones), keratins, or CD57. Follow-up data were available for 25 individuals (median follow-up period, 6 yrs 7 mos) with regrowth of the tumor or persistent disease documented in 17 (72%). The following events were more common in the group with recurrent or persistent disease: congenital onset, male sex, hand and foot location, incomplete excision, and mitotic activity in the fibroblastic element. Although it is likely this tumor comprises part of the spectrum of what has been referred to in the literature as infantile/juvenile fibromatosis, its clinicopathologic features and, in particular, its distinctive tendency to contain fat as an integral component, warrant separate classification as a "lipofibromatosis."

#714 High dose chemotherapy (HDC) and hematopoietic stem cell transplant (HSCT) in advanced pediatric soft tissue tumors (STT)

Mascarenhas, L.; Butturini, A.; EpsteinEderich, A.; Seeger, R.; Villablanca, J.; Siegel, S. Author Information

Recent advances in the diagnosis of pediatric soft‐tissue tumors

Medical and Pediatric OncologyVolume 32, Issue 5 p. 373-376 Topical Topics Recent advances in the diagnosis of pediatric soft-tissue tumors Scott E. Kilpatrick MD, Corresponding Author Scott E. Kilpatrick MD scott_kilpatrick@med.unc.edu Department of Pathology, University of North Carolina at Chapel Hill, Chapel Hill, North CarolinaDepartment of Pathology, University of North Carolina, CB#7525, Brinkhous-Bullitt Building, Chapel Hill, NC 27599Search for more papers by this authorA. Julian Garvin MD, PhD, A. Julian Garvin MD, PhD Department of Pathology, Wake Forest University Medical Center, Winston-Salem, North CarolinaSearch for more papers by this author Scott E. Kilpatrick MD, Corresponding Author Scott E. Kilpatrick MD scott_kilpatrick@med.unc.edu Department of Pathology, University of North Carolina at Chapel Hill, Chapel Hill, North CarolinaDepartment of Pathology, University of North Carolina, CB#7525, Brinkhous-Bullitt Building, Chapel Hill, NC 27599Search for more papers by this authorA. Julian Garvin MD, PhD, A. Julian Garvin MD, PhD Department of Pathology, Wake Forest University Medical Center, Winston-Salem, North CarolinaSearch for more papers by this author First published: 07 April 1999 https://doi.org/10.1002/(SICI)1096-911X(199905)32:5<373::AID-MPO11>3.0.CO;2-4Citations: 9AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume32, Issue5May 1999Pages 373-376 RelatedInformation

Recent advances in the diagnosis of pediatric soft-tissue tumors.

Recent advances in the diagnosis of pediatric soft-tissue tumors.

Cloning and Characterization of a NovelRab-Family Gene,Rab36,within the Region at 22q11.2 That Is Homozygously Deleted in Malignant Rhabdoid Tumors

Malignant rhabdoid tumors (MRTs) are rare, pediatric soft-tissue tumors. Homozygous deletions at chromosome 22q11.2 are a recurrent cytogenetic characteristic of MRTs, an indication that this locus may harbor one or more genes conferring tumor-suppressor activity. We constructed a deletion map of the relevant part of 22q11.2 from a panel of seven MRT cell lines, and isolated a novel gene from the center of the region. As it showed a high degree of sequence homology to genes of theRabfamily, we designated itRab36.The protein encoded byRab36was localized at the Golgi body. Sequencing ofRab36cDNAs from three cell lines that retained at least one allele of this gene revealed no nonsense or frameshift mutations. Experiments to induce over-expression ofRab36by transfection to an MRT cell line similarly failed to justify designation of this gene as a tumor suppressor that would contribute to tumorigenesis by a loss-of-function mechanism.

Pediatric Soft Tissue Tumors: A Clinical, Pathological and Therapeutic Approach

Pediatric Soft Tissue Tumors: A Clinical, Pathological and Therapeutic Approach

Tumor karyotype differentiates lipoblastoma from liposarcoma

Lipoblastoma is a rare benign pediatric soft tissue tumor that may be difficult to distinguish from a myxoid liposarcoma clinically or histologically. The authors present a case of a progressively growing, locally invasive soft tissue tumor in a child. Tissue culture for cytogenetic study showed a breakpoint in the long arm of chromosome 8. A review of the literature showed seven case reports of lipoblastoma karyotype, six of which had a similar breakpoint in chromosome 8. This distinguishes it from the histologically alike myxoid liposarcoma, the karyotype of which typically contains the clonal anomaly t(12;16)(q13:p11). The authors recommend that when performing a biopsy of a childhood adipose tumor with unusual features, such as progressive or invasive growth, that fresh tissue be submitted for cell culture. The tumor karyotype will, in most cases, aid in differentiating lipoblastoma from myxoid liposarcoma.

Detection of Gene Fusions in Rhabdomyosarcoma by Reverse Transcriptase-Polymerase Chain Reaction Assay of Archival Samples

Alveolar rhabdomyosarcoma is a pediatric soft-tissue tumor that is often difficult to distinguish from other small round-cell tumors. The PAX3-FKHR and PAX7-FKHR gene fusions that result from chromosomal translocations in this tumor provide potential molecular diagnostic markers. To apply these molecular markers to commonly available archival material, we used reverse transcriptase-polymerase chain reaction and oligonucleotide hybridization methodology to develop an assay capable of identifying PAX3-FKHR and PAX7-FKHR fusion transcripts in formalin-fixed, paraffin-embedded tissue. Use of a control assay for wild-type FKHR mRNA indicated that RNA was successfully isolated, reverse-transcribed, and amplified in 15 of 16 archival cases. Comparison of assay results for the PAX3-FKHR and PAX7-FKHR fusions with standard molecular assays of paired frozen material revealed that all eight cases of known fusion-positive rhabdomyosarcoma were correctly identified and distinguished as PAX3-FKHR or PAX7-FKHR. The seven cases of known fusion-negative rhabdomyosarcoma showed no evidence of either product. These results indicate that we have developed a molecular assay that accurately identifies the fusion transcripts characteristic of alveolar rhabdomyosarcoma in archival samples. This assay will be useful for diagnosis and for retrospective clinicopathologic correlative studies.

Synovial sarcoma of childhood and adolescence. Report of the German CWS-81 study.

Synovial sarcoma is the third most common pediatric soft tissue tumor. It requires an aggressive approach to achieve a cure. However, optimal treatment modalities adapted to disease extension and histologic variants have not been determined because there is little information about prospectively treated patients. A multicenter trial for soft tissue sarcomas (Protocol CWS 81) was conducted in West Germany between 1981-1985, and 31 patients with synovial sarcoma were registered. Treatment included multiagent chemotherapy and irradiation after initial tumor excision or biopsy. The male-female ratio in this group was 1:1.6 with a median age of 14 years (range, 1-19 years). The median follow-up time after diagnosis was 101 months (range, 77-131 months). The overall event-free survival (EFS) for patients with synovial sarcoma was 74.2% at 5 years. Group I-II tumors had a significantly better prognosis than those in Group III-IV (EFS at 5 years 84.4% and 58.3%, respectively; P = 0.024). Small tumors (< 5 cm) responded better than larger tumors (> or = 5 cm; EFS, 93% versus 58%; P = 0.029). Synovial sarcoma involved the extremities in 28 patients who had a better outcome compared with those with extremity rhabdomyosarcoma in this study (EFS for Group I-IV was 82% versus 24%, P = 0.001). The results appeared superior to previous experience using radical surgery alone and suggested that after initial, nonmutilating surgery, adjuvant chemotherapy, and irradiation contributed to the improved long-term survival.

Localization of the t(2;13) breakpoint of alveolar rhabdomyosarcoma on a physical map of chromosome 2

A characteristic translocation t(2;13)(q35;q14) has been previously identified in the pediatric soft tissue tumor alveolar rhabdomyosarcoma. We have assembled a panel of lymphoblast, fibroblast, and somatic cell hybrid cell lines with deletions and unbalanced translocations involving chromosome 2 to develop a physical map of the distal 2q region. Twenty-two probes were localized on this physical map by Southern blot analysis of the mapping panel. The position of these probes with respect to the t(2;13) rhabdomyosarcoma breakpoint was then determined by quantitative Southern blot analysis of an alveolar rhabdomyosarcoma cell line with two copies of the derivative chromosome 13 and one copy of the derivative chromosome 2 and by analysis of somatic cell hybrid clones derived from an alveolar rhabdomyosarcoma cell line. We demonstrate that the t(2;13) breakpoint is situated within a map interval delimited by the distal deletion breakpoint in fibroblast line GM09892 and the t(X;2) breakpoint in somatic cell hybrid GM11022. Furthermore, from a comparison of our data with the linkage map of the syntenic region on mouse chromosome 1, we conclude that the t(2;13) breakpoint is most closely flanked by loci INHA and ALPI within this map interval.