Primitive Myxoid Mesenchymal Tumor Of Infancy Research Articles

Primitive myxoid mesenchymal tumor of infancy, an enigmatic entity: A case report.

Primitive myxoid mesenchymal tumor of infancy (PMMTI) is a rare soft tissue neoplasm of intermediate malignant potential occurring predominantly in infants and younger children. It can show aggressive local infiltration of surrounding structures and frequent relapses but rare metastasis. Morphologically, it is characterized by a proliferation of immature mesenchymal cells in a myxoid background with mild cytologic atypia and branching vessels. The tumor cells demonstrate immunoreactivity with vimentin and BCOR, however, are negative for more specific lineage markers. Its molecular hallmark is BCOR-internal tandem duplication. Previously classified as infantile fibrosarcoma/undifferentiated sarcoma, the association with BCOR-ITD has led to its reclassification as part of a distinct entity-"Sarcoma with BCOR Genetic Alterations"-in the 2020 WHO Classification of Soft Tissue Tumours. Here is a report of a case of a 2-year-old boy with a recurrent scalp mass identified as a primitive myxoid mesenchymal tumor of infancy.

Primitive Myxoid Mesenchymal Tumor of Infancy: A Case Report

Primitive myxoid mesenchymal tumor of infancy (PMMTI) is a rare malignant tumor that occurs in the soft tissue in early childhood. This malignant tumor can occur in various parts of the body, such as the trunk, extremity, and head & neck area, and is characterized by aggressive local infiltration. There is no standardized treatment so far because this tumor is very rare worldwide. Still now, the principle of treatment so far is complete surgical resection. We performed a surgical treatment for a 3-year-old PMMTI patient who visited the hospital with an incidentally discovered mass in the posterior neck. If surgical treatment is selected as the treatment for PMMTI, it is thought that resection with sufficient margins during surgery will help reduce recurrence. In addition, since local recurrence is frequent and the average recurrence- free duration is short, careful short-term follow-up is necessary.

Fine needle aspiration cytology of the primitive myxoid mesenchymal tumor of infancy.

Primitive myxoid mesenchymal tumor of infancy (PMMTI) is a recently described entity, previously included under the umbrella of undifferentiated sarcomas. These tumors are notorious for recurrence, chemoresistance and may even metastasize. We describe here, for the first time, the cytomorphology of PMMTI. Further, we discuss the morphological differentials and relevant immunocytochemical markers to reach a correct diagnosis. Knowledge about the distinctive cytomorphological features with characteristic immunocytochemistry is the key to the challenging diagnosis of PMMTI. Establishing the diagnosis on cytology is not difficult in cases of recurrence when such a history is forthcoming. These tumors are a rarity, and awareness of cytomorphology and employment of ancillary techniques is diagnostic, guiding the appropriate therapeutic management.

Primitive myxoid mesenchymal tumor of infancy: Case report and review of the literature

Primitive myxoid mesenchymal tumor of infancy (PMMTI) is an extremely rare soft tissue tumor with only a few cases. Herein, we report a case of 5-months-old girl presenting with a soft tissue mass on the sole of the left foot that recurred 2months after a first resection. The Doppler ultrasound imaging showed abundant blood flow in the tumor. Magnetic resonance imaging (MRI) showed a well demarcated tumor on the sole of the left foot. The surgically resected tumor consisted of primitive mesenchymal tumor cells dispersed in a myxoid background with delicate small blood vessels. Immunohistochemically, tumor cells expressed vimentin but were negative for AE1/AE3, Desmin, Muscle-Specific Actin, MyoD1, Myogenin, CD34, S-100 protein and CD99. Fluorescence in situ hybridization (FISH) showed absence of chromosomal translocation involving SYT and ETV6. Thus, the patient was diagnosed with a primitive myxoid mesenchymal tumor of infancy. To our knowledge, this is the first case of PMMTI affecting the sole of the foot.

Assessment of BCOR Internal Tandem Duplications in Pediatric Cancers by Targeted RNA Sequencing

Alterations in the BCOR gene, including internal tandem duplications (ITDs) of exon 15 have emerged as important oncogenic changes that define several diagnostic entities. In pediatric cancers, BCOR ITDs have recurrently been described in clear cell sarcoma of kidney (CCSK), primitive myxoid mesenchymal tumor of infancy (PMMTI), and central nervous system high-grade neuroepithelial tumor with BCOR ITD in exon 15 (HGNET-BCOR ITDex15). In adults, BCOR ITDs are also reported in endometrial and other sarcomas. The utility of multiplex targeted RNA sequencing for the identification of BCOR ITD in pediatric cancers was investigated. All available archival cases of CCSK, PMMTI, and HGNET-BCOR ITDex15 were collected. Each case underwent anchored multiplex PCR library preparation with a custom-designed panel, with BCOR targeted for both fusions and ITDs. BCOR ITD was detected in all cases across three histologic subtypes using the RNA panel, with no other fusions identified in any of the cases. All BCOR ITDs occurred in the final exon, within 16 codons from the stop sequence. Multiplex targeted RNA sequencing from formalin-fixed, paraffin-embedded tissue is successful at identifying BCOR internal tandem duplications. This analysis supports the use of anchored multiplex PCR targeted RNA next-generation sequencing panels for identification of BCOR ITDs in pediatric tumors. The use of post-analytic algorithms to improve the detection of BCOR ITD using DNA panels was also explored.

Specific and Sensitive Diagnosis of BCOR-ITD in Various Cancers by Digital PCR.

BCOR is an epigenetic regulator altered by various mechanisms including BCOR-internal tandem duplication (BCOR-ITD) in a wide range of cancers. Six different BCOR-ITD in the 3’-part of the coding sequence of exon 15 have been reported ranging from 89 to 114 bp in length. BCOR-ITD is a common genetic alteration found in clear cell sarcoma of the kidney and primitive myxoid mesenchymal tumor of infancy (PMMTI) and it characterizes a new type of central nervous system tumor: “CNS tumor with BCOR-ITD”. It can also be detected in undifferentiated round cell sarcoma (URCS) and in high-grade endometrial stromal sarcoma (HGESS). Therefore, it is of utmost importance to search for this genetic alteration in these cancers with the most frequent technique being RNA-sequencing. Here, we developed a new droplet PCR assay (dPCR) to detect the six sequences characterizing BCOR-ITD. To achieve this goal, we used a single colored probe to detect both the duplicated region and the normal sequence that acts as a reference. We first generated seven synthetic DNA sequences: ITD0 (the normal sequence) and ITD1 to ITD6 (the duplicated sequences described in the literature) and then we set up the optima dPCR conditions. We validated our assay on 19 samples from a representative panel of human tumors (9 HGNET-BCOR, 5 URCS, 3 HGESS, and 2 PMMTI) in which BCOR-ITD status was known using at least one other method including RNA sequencing, RT-PCR or DNA-methylation profiling for CNS tumors. Our results showed that our technique was 100% sensitive and specific. DPCR detected BCOR-ITD in 13/19 of the cases; in the remaining 6 cases additional RNA-sequencing revealed BCOR gene fusions. To conclude, in the era of histomolecular classification of human tumors, our modified dPCR assay is of particular interest to detect BCOR-ITD since it is a robust and less expensive test that can be applied to a broad spectrum of cancers that share this alteration.

Primitive myxoid mesenchymal tumor of infancy. Review of literature

Primitive myxoid mesenchymal tumor of infancy (PMMTI) is an aggressive tumor with a high rate of local recurrence, rare metastasis and poor response to chemotherapy.PMMTI is a rare soft-tissue sarcoma that preferentially affects infants. It is isolated from the group of infantile fibrosarcomas or myofibroblastic tumors. PMMTI differs from other tumors in the clinical course, morphological features and primarily molecular genetic changes. ETV6-NTRK3 gene fusion is characteristic of infantile fibrosarcomas. However, it is not detected in patients with PMMTI. BCOR ITD had been described in patients with PMMTI and it allowed to define this tumor from the group of infantile fibrosarcomas.Unified treatment approaches have not been identified for this tumor yet. Radical surgical removal is preferred treatment. BCOR ITD is a target. Nowadays search for targeted drugs is ongoing and it could help to solve the problem of PMMTI treatment.

“Primitive myxoid mesenchymal tumor of infancy” - A rare childhood soft-tissue tumor of the mandible

Primitive myxoid mesenchymal tumor of infancy (PMMTI) is an extremely rare soft-tissue tumor of childhood. We report a case of an 18-month-old male child diagnosed with PMMTI of the mandible. Till now

Recurrent BCOR Internal Tandem Duplication and YWHAE-NUTM2B Fusions in Soft Tissue Undifferentiated Round Cell Sarcoma of Infancy: Overlapping Genetic Features With Clear Cell Sarcoma of Kidney.

Soft tissue undifferentiated round cell sarcoma (URCS) occurring in infants is a heterogenous group of tumors, often lacking known genetic abnormalities. On the basis of a t(10;17;14) karyotype in a pelvic URCS of a 4-month-old boy showing similar breakpoints with clear cell sarcoma of kidney (CCSK), we have investigated the possibility of shared genetic abnormalities in CCSK and soft tissue URCS. Most CCSKs are characterized by BCOR exon 16 internal tandem duplications (ITDs), whereas a smaller subset shows YWHAE-NUTM2B/E fusions. Because of overlapping clinicopathologic features, we have also investigated these genetic alterations in the so-called primitive myxoid mesenchymal tumor of infancy (PMMTI). Among the 22 infantile URCSs and 7 PMMTIs selected, RNA sequencing was performed in 5 and 2 cases, with frozen tissue, respectively. The remaining cases with archival material were tested for YWHAE-NUTM2B/E by fluorescence in situ hybridization (FISH) or reverse transcription-polymerase chain reaction (RT-PCR), and BCOR ITD by PCR. A control group of 4 CCSKs and 14 URCSs in older children or adults without known gene fusion and 20 other sarcomas with similar histomorphology or age at presentation were also tested. A YWHAE-NUTM2B fusion was confirmed in the index case by FISH and RT-PCR, whereas BCOR ITD was lacking. An identical YWHAE-NUTM2B fusion was found in another URCS case of a 5-month-old girl with a back lesion. The remaining cases and control group lacked YWHAE gene rearrangements; instead, consistent BCOR ITDs, similar to CCSK, were found in 15/29 (52%) infantile sarcoma cases (9/22 infantile URCS and 6/7 PMMTI). In the control cohort, BCOR ITD was found only in 3 CCSK cases but not in the other sarcomas. Histologically, URCS with both genotypes and PMMTI shared significant histologic overlap, with uniform small blue round cells with fine chromatin and indistinct nucleoli. A prominent capillary network similar to CCSK, rosette structures, and varying degree of myxoid change were occasionally seen. BCOR ITD-positive tumors occurred preferentially in the somatic soft tissue of the trunk, abdomen, and head and neck, sparing the extremities. RNAseq showed high BCOR mRNA levels in BCOR ITD-positive cases, compared with other URCSs. In summary, we report recurrent BCOR exon 16 ITD and YWHAE-NUTM2B fusions in half of infantile soft tissue URCS and most PMMTI cases, but not in other pediatric sarcomas. These findings suggest a significant overlap between infantile URCS and CCSK, such as age at presentation, histologic features, and genetic signature, thus raising the possibility of a soft tissue counterpart to CCSK.

Undifferentiated myxoid lipoblastoma with PLAG1–HAS2 fusion in an infant; morphologically mimicking primitive myxoid mesenchymal tumor of infancy (PMMTI)—diagnostic importance of cytogenetic and molecular testing and literature review

Lipoblastoma is a benign myxoid neoplasm arising in young children that typically demonstrates adipose differentiation. It is often morphologically indistinguishable from primitive myxoid mesenchymal tumor of infancy (PMMTI), which is characterized by a well-circumscribed myxoid mass with a proliferation of primitive mesenchymal cells with mild cytologic atypia. PMMTI occurs in the first year of life and is known to have locally aggressive behavior. No specific genetic rearrangements have been reported to date. In contrast, the presence of PLAG1 (Pleomorphic Adenoma Gene 1) rearrangement is diagnostic for lipoblastoma. We hereby demonstrate the combined application of multiple approaches to tackle the diagnostic challenges of a rapidly growing neck tumor in a 3-month-old female. An incisional tumor biopsy had features of an undifferentiated, myxoid mesenchymal neoplasm mimicking PMMTI. However, tumor cells showed diffuse nuclear expression by immunohistochemical (IHC) stain. Conventional cytogenetic and fluorescence in situ hybridization (FISH) analyses as well as next generation sequencing (NGS) demonstrated evidence of PLAG1 rearrangement, confirming the diagnosis of lipoblastoma. This experience warrants that undifferentiated myxoid lipoblastoma can mimic PMMTI, and the combination of cytogenetic and molecular approaches is essential to distinguish these two myxoid neoplasms. Literature on lipoblastomas with relevant molecular and cytogenetic findings is summarized. Our case is the first lipoblastoma diagnosed with a PLAG1 fusion defined by NGS technology.

Transformation of a Primitive Myxoid Mesenchymal Tumor of Infancy to an Undifferentiated Sarcoma

An 8-month-old girl underwent surgical resection of a cervical mass with histologic diagnosis of a primitive myxoid mesenchymal tumor of infancy (PMMTI). More than 5 years after the initial surgical intervention, the tumor recurred locally, with numerous distant metastases. The histologic morphology of this tumor was compatible with a diagnosis of an undifferentiated high-grade sarcoma. PMMTI is a recently described poorly differentiated fibroblastic soft-tissue tumor of infancy, of at least borderline biological behavior, characterized by local recurrence and a potential to metastasize. We present here the first case of a transformation of a PMMTI into an undifferentiated high-grade sarcoma.

Primitive Myxoid Mesenchymal Tumor of Infancy With Rosettes

Primitive myxoid mesenchymal tumor of infancy (PMMTI) is a relatively recently described tumor arising in infants and demonstrating a unique histomorphology. We present an unusual case of PMMTI with rosettes, a hitherto undescribed finding in the reported cases. We also present the cytogenetic and ultrastructural findings of this tumor and review the literature. As awareness of PMMTI increases, additional clinical data and histopathologic findings will aid in the morphologic and behavioral characterization of this neoplasm.

Case report of primitive myxoid mesenchymal tumor of infancy in a 2-month-old infant

Primitive myxoid mesenchymal tumor of infancy (PMMTI) is rare with aggressive clinical course and a new category of pediatric fibroblastic–myofibroblastic tumor. It previously may have been included under the diagnostic categories of congenital-infantile fibrosarcoma, undifferentiated sarcoma or infantile fibromatosis. The tumors occurred on the trunk, extremities and head and neck. There are no reported case of this tumor occurring in the facial–buccal region. After surgery and regular follow up the patient is still alive until 3 years old now.

Primitive Myxoid Mesenchymal Tumor of Infancy

Soft tissue sarcomas in the first year of life are rare, and the most common sarcomas in infancy are embryonal rhabdomyosarcoma, Ewing sarcoma/primitive neuroectodermal tumor, congenital infantile fibrosarcoma, and primitive sarcomas such as undifferentiated sarcoma. In this study, we report 6 cases of a primitive myxoid mesenchymal tumor of infancy (PMMTI), which previously may have been included under the diagnostic categories of congenital-infantile fibrosarcoma or infantile fibromatosis. PMMTI occurred in 6 infants, 3 of whom had a congenital presentation of a soft tissue mass. All patients were otherwise healthy. The tumors occurred on the trunk, extremities, and head and neck. Grossly, the tumors were nonencapsulated and had a multinodular appearance with focal infiltrative growth, a white fleshy cut surface, and a tumor diameter ranging from 2 to 15 cm. Histologically, a diffuse growth of primitive spindle, polygonal, and round cells occurred in a myxoid background. The tumor cells were arranged in a vaguely nodular pattern with peripheral collagenized stroma, higher cellularity at the periphery, and a delicate vascular network in the background. Immunohistochemically, the tumors displayed diffuse reactivity for vimentin and no reactivity for smooth muscle actin, muscle specific actin, desmin, S-100 protein, or myogenin. Electron microscopy documented a poorly differentiated fibroblastic proliferation. Four cases tested negative for the ETV6-NTRK3 gene fusion by RT-PCR. One tumor had a complex karyotypic abnormality with rearrangements involving chromosomes Y, 9, and 3. Three patients had recurrences or metastasis treated with a combination of surgery and chemotherapy. One patient is alive with persistent locally aggressive disease, 2 are alive with no evidence of recurrence, 1 had a recurrence treated surgically without further follow-up information, 1 patient died with persistent tumor and sepsis 6 weeks after diagnosis, and 1 patient was lost to follow-up. The morphologic appearance combined with the ultrastructural features and absence of the typical gene rearrangement of congenital-infantile fibrosarcoma are unique, and we propose that PMMTI represents a new category of pediatric fibroblastic-myofibroblastic tumor.