Congenital Infantile Fibrosarcoma Research Articles

Magnetic Resonance Imaging Features of Congenital Infantile Fibrosarcoma.

Background Congenital/infantile fibrosarcoma is a rare soft tissue tumor presented in early age of life. It should be considered in the differential diagnosis of the large soft tissue masses especially in the extremities at the age of infancy. These tumors frequently are misdiagnosed at birth as hemangioma. Histologically, they can resemble their adult counterparts and they are characterized by the chromosomal translocation t(12;15) (p13;q25) resulting in the ETV6-NTRK3 gene fusion. Objective A retrospective review of the MRIfeatures of histopathology-proven congenital/infantile fibrosarcoma provides our own institutional experience and supports the limited radiology literaturewritten about this disease. Material and method The list of our patients is obtained after reviewing our radiology and pathology database in the period between June 1st, 2007 and May 31st, 2017 (10 years) at King Faisal Specialist Hospital & Research Center, Riyadh. Phrases used to search in our MRI examinations database are: congenital infantile fibrosarcoma, infantile fibrosarcoma, juvenile fibrosarcoma, soft tissue sarcoma, malignant soft tissue mass, sarcomatous soft tissue mass, fibrosarcoma, spindle cell sarcoma, myomatous sarcoma. Result In our database and picture archiving and communication system (PACS) during the period of the study, the word (fibrosarcoma) was mentioned in the radiology report of 182 patients. Only four cases were histopathologically proven to be a congenital/infantile fibrosarcoma and had completed their own MR exams - three of them were primary/new cases, males with an age range between 0 days and 5 months (median age: 5 months). The fourth case was a female with a history of 1st presentation at the age of one month and proved by histopathology examination but there was no available imaging at that time; however, tumor recurrence in the same patient was at the age of 4 years with available MR imaging and pathology sample. Conclusion Congenital infantile fibrosarcoma is a rare entity that has no specific MRI findings. However, it should be always considered as part of the differential diagnosis of congenital soft tissue masses with aggressive behavior.

Molar‐incisor‐malformation in a paediatric cancer patient: Case report

AbstractAimTo report a case of molar‐incisor‐malformation (MIM) in a 7‐year‐old boy with a history of congenital infantile fibrosarcoma of the upper chest, which was surgically treated, without adjuvant radio/chemotherapy.Material and MethodsThe boy presented with mobility and pain on percussion of the permanent mandibular first molars. The radiographic features were suggestive of MIM. Both teeth were extracted and processed for conventional light microscopic examination and non‐decalcified ground sections.ResultsThe microscopic features confirmed the diagnosis of MIM. Regular follow‐up was recommended.ConclusionsMedical interventions during hospitalization for cancer treatment, other than chemo/radiotherapy, may cause MIM by adversely affecting the function of Hertwig's epithelial root sheath. Regular dental screening in paediatric cancer patients may reveal more MIM cases and help in elucidating its pathogenesis.

Congenital infantile fibrosarcoma: a rare tumor dermatologists should know about

Congenital infantile fibrosarcoma: a rare tumor dermatologists should know about

Сongenital infantile fibrosarcoma with a non-canonical TPM3-NTRK1 fusion transcript: a case report and a literature review

Infantile fibrosarcoma (IFS) is a rare malignant soft tissue tumor characterized by local invasion, a low rate of distant metastasis (1–13%), and manifestation during the first years of life. Overall survival rates range from 89 to 94%, event-free survival rates – from 81 to 84%. Classic IFS is characterized by t(12;15)(p13;q25) translocation resulting in the formation of the ETV6-NTRK3 fusion transcript. However, over the past few years, there have been numerous reports of IFS-like tumors with non-canonical genetic aberrations (BRAF, NTRK1, MET genes) whose prognosis is less predictable. Here we report a rare case of congenital IFS with involvement of subcutaneous fat, indolent course and a non-canonical TPM3-NTRK1 fusion transcript identified in the soft tissue and intradermal tumor components with different histological features. The patient’s parents gave their consent to the use of their child’s data, including photographs, for research purposes and in publications. The literature review explores modern algorithms for the diagnosis and treatment of IFS in children, including the use of new therapies, such as tropomyosin receptor kinase inhibitors, as well as algorithms for detecting NTRK1, NTRK2, NTRK3 gene rearrangements in solid neoplasms in general, and soft tissue tumors in particular.

Congenital infantile fibrosarcoma of the abdominal wall: A case report

Abstract Congenital infantile sarcoma is a rare tumor. Any part of the body can be affected, but upper and lower extremities are common sites of the disease. Diagnosis is reached by clinical presentation, radiological findings, immunohistochemical evaluation and molecular detection of chromosomal abnormality associated with the disease. Differential diagnosis depends on tumor location. Surgical excision is the treatment of choice. Chemotherapy can be of value when complete surgical resection is not possible. Radiotherapy role is limited and needs further evaluation. Here we present a case of huge congenital infantile sarcoma. To the best of our knowledge, this is the first case in literature reporting congenital infantile sarcoma arising from the abdominal wall.

EPCO-03. REPORT OF NTRK FUSION IN A PEDIATRIC PATIENT WITH SPINAL GANGLIOCYTOMA

Abstract BACKGROUND Gangliocytomas are rare WHO grade 1 central nervous system tumors of neuronal/ mixed neuronal-glial classification that most commonly occur in the cerebrum, favoring the temporal lobe. They are also reported in cerebellum in the setting of Lhermite-Duclos disease. Spinal gangliocytomas are exceedingly rare, constituting 3–10% of reported pediatric cases. Maximal safe surgical resection is the mainstay of therapy, as response to irradiation or traditional chemotherapy is variable. Given the rarity of these tumors, little is known about the molecular makeup or the role of targeted therapy in this population. CASE Our patient presented as a 7-year-old male with thorocolumbar scoliosis. A magnetic resonance imaging (MRI) of his spine incidentally demonstrated a heterogeneously enhancing, expansile solid and cystic intramedullary thoracic mass from T6 through T11. MRI brain did not show any intracranial mass. He subsequently underwent a laminectomy with laminoplasty for the intramedullary mass. Histopathologic analysis confirmed a WHO grade I gangliocytoma with moderately cellular abnormal central neural tissue composed of irregular clusters and cords of mature-appearing neurons in a coarse neuropil background. Because of the unusual location and presentation of his disease, molecular analysis including DNA and RNA sequencing was performed which revealed a somatic BCR-NTRK2 fusion. DISCUSSION NTRK gene fusions are known oncogenic drivers, reported with varying frequency in many pediatric and adult tumors. They are reported in < 1% of adult head and neck cancers but greater than 90% of congenital infantile fibrosarcomas. NTRK fusions are seen in pediatric brain tumors like infantile high grade gliomas, however they have not been previously reported in gangliocytoma. As TRK inhibitors are efficacious in treating a number of NTRK-rearranged malignancies, this novel finding provides a therapeutic option for NTRK fusion positive gangliocytoma where complete surgical resection is not safely possible.

Primitive Myxoid Mesenchymal Tumour of Nose.

Primitive Myxoid Mesenchymal Tumour of Infancy (P.M.M.T.I.) is a locally aggressive myofibroblastic tumour, occurring mostly in the first year of life. Grossly, it occurs as a non-encapsulated, multi-nodular tumour with focal infiltrative growth with a size ranging from 2 to 15cm. It is composed of primitive spindled cells in a myxoid background. It is a low-grade fibroblastic malignancy with low metastatic potential with a high local recurrence rate. On immunohistochemistry, it stains positive for Vimentin. no reactivity for smooth muscle actin, muscle specific actin, desmin, S-100 protein, or myogenin. Electron microscopy documented a poorly differentiated fibroblastic proliferation. The present case is of a P.M.M.T. occurring in the nose of a 3 ½ years old female child. This is the first case reported from Central India. The child had recurrent nasal growth and the excision biopsy was suggestive of intermediate grade fibroblastic neoplasm. The biopsy, on IHC staining, was positive for Vimentin and CD99 and negative for S-100, CD-34 and Desmin, favouring the diagnosis of P.M.M.T. The child had a total of three recurrence of growth after local excision before diagnosis was established. In the prior two surgeries, the histopathological analysis reported it as a benign nasal polyp. After the third surgery, the specimen was sent for IHC. Immunohistochemical stains helped in differentiating it from congenital infantile fibrosarcomas, a similar type of mesodermal tumour. The present case of Primitive myxoid mesenchymal tumour following IHC stains were positive for Vimentin, CD-99, CD-117 and NESTIN, pointing to the primitive nature of the tumour. It was negative for the neural marker. Since it is chemo resistant, the preferred method of treatment is wide surgical excision.

Congenital infantile fibrosarcoma of soft tissues of the chest wall on the left (description of the clinical case and literature review)

Infantile fibrosarcoma (IF) is a rare soft tissue sarcoma that occurs with a frequency of 1% of all cases of malignant neoplasms in children in the first year of life. IF most often affects the soft tissues of the upper and lower extremities. Rare localizations include the trunk, the head and neck, and the gastrointestinal tract. The article describes a rare clinical case of congenital IF of soft tissues of the chest wall in a newborn, as well as a literature review.

A RARE PRESENTATION OF CONGENITAL INFANTILE FIBROSARCOMA OF THE PELVIS- IMAGING WORK UP WITH HISTOPATHOLOGICAL CORRELATION.

Congenital Infantile fibrosarcoma is a rare tumor in children with limited information on imaging features available in the literature. It is a tumor of mesodermal origin, most commonly affecting the lower limbs. In this article, we report a case of congenital infantile fibrosarcoma in a 4-year-old child which mimicked as a sacrococcygeal teratoma of the pelvis.

Paraspinal Congenital Infantile Fibrosarcoma: A Case Report

Congenital infantile fibro-sarcomas (CIFS) are rare, locally aggressive mesenchymal tumors that usually develop from soft tissue of distal extremities. CIFS arising from paraspinal region are extremely rare and only few cases have been reported. A left thoracic paraspinal swelling in a female fetus was noted on 20-week antenatal scan of a primigravida. The swelling was monitored with regular antenatal scans. The baby was born at term and was well at birth. Serum AFP and Beta HCG were within normal age limits. MRI scan confirmed an aggressive tumor infiltrating the paraspinal muscles but not the spinal cord. The mass grew very rapidly in size within a few days, and was excised on day 7 of life. Histopathology and Immunohistochemistry diagnosed the mass to be a Fibrosarcoma. No chemotherapy or radiotherapy was given. The baby is well with no recurrence or residual deformity or neurological deficit after 18 months of follow up.Paraspinal CIFS are extremely rare but can be detected antenatally as early as 20 weeks of gestation. Complete surgical excision is the treatment of choice.

Massive Fetal Transfusion During an Emergency Ex Utero Intrapartum Treatment for a Congenital Infantile Fibrosarcoma: A Case Report

Although originally described to assist airway management of fetal congenital malformations with life-threatening airway obstruction, the indications for an ex utero intrapartum treatment (EXIT) have expanded to include surgical resection of lesions that are potentially incompatible with life in the absence of uteroplacental circulatory support. We describe the case of an infantile fibrosarcoma (IFS) that presented with fetal hydrops and was successfully managed with an emergency EXIT that necessitated the initiation of a massive fetal blood transfusion both with and without the support of uteroplacental circulation.

Cervical congenital infantile fibrosarcoma: a case report

BackgroundCongenital infantile fibrosarcoma is a rare mesenchymal tumor seen in children as well as adults. The congenital variety is rare and out of the reported cases only one case sited in the neck has been reported so far. Another such case is presented here who was successfully managed.Case presentationA 3-month-old Hindu baby boy presented with a congenital neck swelling. The apparent clinical diagnosis was lympho-venous malformation. With a remote possibility of malignancy, an excisional biopsy was done. Histopathology revealed congenital infantile fibrosarcoma.ConclusionA successful excision of cervical congenital infantile fibrosarcoma has not been reported. This diagnosis should be kept as a possibility in all congenital cervical swellings. These are commonly misdiagnosed as lympho-venous malformations and histopathology is confirmatory.

Molecular characterization of cancers with NTRK gene fusions

Targeted inhibitors of neurotropic tyrosine kinases are highly effective in selected patients with gene fusions involving NTRK1, NTRK2, or NTRK3. These fusions are consistently detected in rare cancer types (e.g., secretory breast carcinoma and congenital infantile fibrosarcoma), but the occurrence of NTRK fusions in common cancers and their relationship to other therapy biomarkers are largely unexplored. Tissue samples from 11,502 patients were analyzed for 53 gene fusions and sequencing of 592 genes, along with an immunohistochemical evaluation of TrkA/B/C and PD-L1. Thirty-one cases (0.27% of the entire cohort) had NTRK fusions. The most common fusions were ETV6:NTRK3 (n = 10) and TPM3:NTRK1 (n = 6). Gliomas had the highest number of NTRK fusions (14/982, 1.4%), most commonly involving NTRK2 (n = 9). Seventeen non-glioma cases with NTRK fusions included carcinomas of the lungs, thyroid, breast, cervix, colon, nasal cavity, cancer of unknown primary and soft tissue sarcomas. Strong and uniform Trk expression detected with a pan-Trk immunohistochemistry characterized 7/8 NTRK1 fusion cases and 8/9 NTRK2 fusion cases, while NTRK3 fused cases were positive in 6/11 (55%) of cases. 29% of NTRK fusion cases had no other pathogenic genomic alteration. PD-L1 expression was observed in 23% of NTRK fused cases while high tumor DNA microsatellite instability was detected in two cases. We confirm the rarity of NTRK genes fusions outside the brain malignancies. NTRK inhibitors alone or combined with immune checkpoint inhibitors may be a therapeutic option for a substantial proportion of these patients. Strategies for detection of the NTRK fusion-driven cancers may include immunohistochemistry, but gene fusion detection remains the most reliable tool.

Congenital Infantile Fibrosarcoma in the Premature Infant.

Congenital infantile fibrosarcoma (CIF) is rare and represents less than 1% of all childhood cancers. It is a tumor that originates in the connective fibrous tissue found at the ends of long bones and then spreads to other surrounding soft tissues. These lesions are typically large, grow rapidly, and can often be mistaken for teratomas. Diagnosis is confirmed by pathology, where cellular proliferation of fibroblasts occurs. Imaging is an important part of the diagnosis, which includes the use of magnetic resonance imaging and/or computed tomography scan. Although surgical resection is the primary treatment, chemotherapeutic agents may be used as adjuvant therapy. To describe modalities for accurate diagnosis and treatment of CIF. PubMed was searched using terms "congenital infantile fibrosarcoma" and "infantile fibrosarcoma." Eleven relevant, English language articles were identified and utilized in the preparation of this case presentation. Complications addressed in this case presentation are prenatal diagnostic challenges, pharmacologic interventions in the setting of prematurity, immunosuppression, and acute liver and renal failure. Pharmacologic treatments will include chemotherapy agents, antimicrobial agents, as well as granulocyte colony-stimulating factor for immunosuppression. Nursing challenges included positioning and integumentary disturbances. Utilization of diagnostic imaging and pathology to accurately identify and diagnose CIF is essential. Safety and efficacy of chemotherapeutic agents in premature infants with CIF need to be established.

Congenital Infantile Fibrosarcoma of the Tongue: Case Report and Review of the Literature

Introduction: Congenital infantile fibrosarcoma is often misdiagnosed. It may be more common than noted in the literature. We present an unusual case of paediatric head and neck fibrosarcoma.
 Methods: Restrospective case report and literature review.
 Results: We report the surgical management of a fibrosarcoma of the tongue in an 8-month-old child where neo-adjuvant chemotherapy was unsuccessful.
 Conclusion: Surgical resection is the mainstay of treatment, in the head and neck region where critical structures are close to the tumour, complete resection with wide margins can be difficult. The role of chemotherapy is yet to be defined.

Recurrent and metastatic congenital mesoblastic nephroma: where does the evidence stand?

Fifty years ago, Bolande described Congenital Mesoblastic Nephroma (CMN) as a benign lesion. Unexpected aggressive clinical behaviors prompted a sub-classification based on histology. Recent molecular genetic evidence has identified the aggressive cellular variant to be the renal manifestation of congenital infantile fibrosarcoma. We submit a reappraisal and analysis of the available literature on recurrent and metastatic CMN. An electronic search of PubMed, MEDLINE, EMBASE, and Scopus yielded 38 children with local recurrence and/or metastases. Of the 38 children with local recurrence and/or metastasis, 59% were girls. Median time to recurrence was 6months (range 1-12months). The commonest sites of metastases were the lung (39%) and liver (29%). Fifty percent of these children died of disease. The outcome of additional chemotherapy (p=0.5) did not differ from that of surgery alone. The choice of chemotherapy did not influence the outcome (p=0.6). Recurrence and metastasis in cellular CMN are much more common than described earlier and carry a high mortality. Children with cellular and mixed CMN require close clinical and radiological follow-up for a minimum of 12months after primary surgery. Surgery is the mainstay of the treatment of recurrent and metastatic lesions. Neoadjuvant chemotherapy is recommended only if the lesion is inoperable. Targeted therapy may be an option in treatment of refractory cases.

Infantile NTRK-associated Mesenchymal Tumors.

Pediatric fibroblastic/myofibroblastic lesions are a relatively common group of tumors with varying morphologies, for which the molecular mechanisms are becoming increasingly well characterized. Congenital infantile fibrosarcoma (CIFS), perhaps the most well studied of these lesions is characterized by a recurrent ETV6-NTRK3 gene fusion. However, a notable subset of locally aggressive congenital/infantile soft tissue lesions with similar morphologic features to CIFS, have not to-date, shown evidence of any canonical molecular aberration. We describe 6 patients with mesenchymal tumors composed of infiltrative fibroblastic/myofibroblastic tumor cells and showing a morphologic spectrum of features much analogous to that previously described in CIFS but without ETV6 fusion transcripts. These tumors lacked a uniform immunoprofile, but showed variable expression of CD34, S100, smooth muscle actin, and CD30. All patients first developed a mass in infancy (≤2 months of age). Using next-generation DNA sequencing, TMP3-NTRK1 fusions were identified in 4 cases, an LMNA-NTRK1 fusion in one case, and a variant EML4-NTRK3 fusion in one case. Similar to infantile fibrosarcoma, these tumors were locally aggressive (with local recurrences if incompletely excised) and rarely metastasized (lung metastases in one patient). Proper identification of these tumors including investigation for NTRK family gene rearrangements is essential for diagnostic accuracy, as well as for clinical management decisions. Given the morbidity associated with radical resection of large soft tissue tumors, children with unresectable, recurrent, and/or metastatic disease may benefit from treatment with NTRK targeted therapies.

Recurrent BCOR internal tandem duplication and BCOR or BCL6 expression distinguish primitive myxoid mesenchymal tumor of infancy from congenital infantile fibrosarcoma

Primitive myxoid mesenchymal tumor of infancy is a rare sarcoma that preferentially affects infants. It can be locally aggressive and rarely metastasizes, but the long-term outcome of children with this tumor is mostly unknown. Histologically, it is characterized by primitive cells with abundant myxoid stroma. Internal tandem duplication of B-cell CLL/lymphoma 6 (BCL6)-interacting co-repressor (BCOR) exon 15 has recently been described in clear cell sarcoma of kidney, central nervous system high-grade neuroepithelial tumor with BCOR alteration, and primitive myxoid mesenchymal tumor of infancy. Herein, we report five cases of primitive myxoid mesenchymal tumor of infancy: three girls and two boys with mean age of 6.5 months. The tumors were located in the paraspinal region (n=3), back (n=1), or foot (n=1) and ranged in size from 2.5 to 10.2 cm. BCOR internal tandem duplication was confirmed by PCR and sequencing in all five cases. The minimally duplicated region consisted of nine residues, which is shorter than was previously reported in other BCOR-associated tumors. To assess the clinical value and specificity of the BCOR internal tandem duplication, a group of 11 ETV6-rearranged congenital infantile fibrosarcomas were evaluated and no BCOR internal tandem duplication was identified in any case. Though not detected in congenital infantile fibrosarcomas, BCOR and BCL6 immunoreactivity was present in >90% of the nuclei of tumor cells in each of the five primitive myxoid mesenchymal tumor of infancy. The presence of BCOR internal tandem duplication in all five primitive myxoid mesenchymal tumors of infancy provides evidence that it is a recurrent somatic abnormality and substantiates the concept that this tumor is a unique sarcoma of infancy. Our findings indicate that identification of BCOR internal tandem duplication and/or nuclear immunoreactivity for BCOR or BCL6 can aid in the diagnosis of primitive myxoid mesenchymal tumor of infancy and help to differentiate it from congenital infantile fibrosarcoma.

Congenital infantile fibrosarcoma mimicking sacrococcygeal teratoma in a Ghanaian infant: A case report and review of the literature

Congenital infantile fibrosarcoma (CIFS) is a rare tumour of childhood accounting for less than 1% of malignant tumours in children. Reports from sub-Saharan Africa are particularly rare and the occurrence in the sacral region mimicking a sacrococcygeal teratoma has not been reported in Africa to the best of our knowledge. The poor predilection of the tumour for distant metastases may contribute to its above average prognosis, but the rarity of systemic antenatal detection of congenital conditions in most parts of Africa may mitigate this good fortune. We report the very rare case of a 9-month-old female infant who presented with a progressively increasing painless sacral mass from birth which was thought to be a sacrococcygeal teratoma clinically but histopathological assessment revealed a CIFS.

Congenital mesoblastic nephroma: a study of 19 cases using immunohistochemistry and ETV6-NTRK3 fusion gene rearrangement

Mesoblastic nephroma (MN) is the most common renal tumour in the first 3 months of life and accounts for 3-5% of all paediatric renal neoplasms. To further understand the morphological variants of MN, we identified 19 cases of MN (five classic, eight cellular and six mixed) and examined each case for markers known to be important in urogenital embryological development (PAX8, WT1 and RCC), stem cell associated markers (Oct 4, CD34 and c-kit), muscle/myofibroblastic markers (muscle specific actin, calponin and h-caldesmon), aberrant transcription factors, cell cycle regulation and other oncogenic proteins (p16, cyclin D1 and beta-catenin). Fluorescence in situ hybridisation (FISH) testing for ETV6-NTRK3 gene fusion/rearrangement revealed further differentiation between the subtypes with ETV6-NTRK3 gene fusion detected in 0/5 of the classic MN, 8/8 of the cellular MN and 5/6 of the mixed MN cohorts, respectively. Our results conclude that cyclin D1 and beta-catenin may be useful markers for differentiating between cellular MN and classic MN when the histology is not conclusive. The absence of expression of stem cell markers and markers involved in urogenital development suggests that MN is not a nephroma and most likely represents a soft tissue tumour, with congenital infantile fibrosarcoma representing cellular MN with a predilection to arise in the kidney. In addition, the immunophenotype and genetic fingerprint of mixed MN most likely represents a heterogenous group of tumours that are mostly cellular type, with areas that are phenotypically less cellular.