Since the first report in 2006, the number of PMMTI cases has not exceeded 40. The biological behavior of PMMTI remains unclear. PMMTI develops in newborns or infants aged less than 1 year. In the 36 cases, 29 cases were less than 1 year old. The oldest patient was 4 years old. 17 cases were male, and 18 cases were female. The incidence had approximately equal men and women. The tumor was mainly located in the torso and limbs, paraspinal, head and neck, and abdominal cavity. In the 29 cases, the tumor sizes ranged from 0.9 cm to 15 cm. 14 tumor cases were larger than 5 cm, accounting for 54%. 12 tumor cases were less than or equal to 5 cm, accounting for 46%. Fourteen out of 26 patients had relapsed or metastasized tumor. Recurrence or metastasis rate reached 56%. The tumors of three patients were incompletely removed because of their adhesion to surrounding tissues. Five patients died (19.2%).
During gross examination, the tumor principally presented as unencapsulated and frequently exhibited focal infiltration. The cut surface usually showed gray-white myxoid. The tumor cells had relatively uniform morphology and consisted of primitive mesenchymal cells in a myxoid background at the microscopic level. The tumor cells were diffusely distributed and were mainly spindle cells. We occasionally found many fat cells and infiltration of focal lymphocytes. The tumor cells had unclear boundaries, fat and spindle-shaped nuclei, homogeneous chromatin, occasional nucleoli, and variable amounts of pale eosinophilic to clear vacuolated cytoplasm.
PMMTI diagnosis was based on morphologic features. Therefore, it should be distinguished from other tumors that occur in infants and young children. Tumors that frequently need to be identified include CIFS, CCSK, ERMS, EWS/PNET, and ISTURCS. CIFS is a pediatric spindle cell tumor of the soft tissues, and the majority of age is before 2 years. CIFS histologically displays sheets of spindle cells, and its myxoid areas are less than those in PMMTI. Molecular and cytogenetic studies have shown that t (12,15) with ETV6-NTRK3 gene fusion occurs in CIFS , but is absent in PMMTI. Bourgeois et al. studied a large series of childhood pediatric spindle cell lesions for ETV6-NTRK3 gene fusions, including 11 cases of CIFS, 13 adult-type fibrosarcoma, and 38 benign spindle cell tumors (including infantile fibromatosis and myofibromatosis). Ten out of 11 cases of CIFS showed the ETV6-NTRK3 gene fusion, whereas none of the 51 other tumors demonstrated this gene fusion .
CCSK is an aggressive primary pediatric renal tumor, and the age of occurrence frequently ranges from 2 years to 3 years . CCSK consists of nests of plump ovoid or spindled cells. Its protein profile is characterized by the expression of only the nonspecific marker vimentin. Some studies have shown that cyclin D1 is helpful in distinguishing CCSK from Wilms tumor, rhabdoid tumor, and metanephric adenoma [24,25].
Few studies have found that BCOR internal tandem duplication (ITD) is found in 85% of CCSK cases . Kao et al. studied 22 ISTURCS, 7 PMMTI, and 4 CCSK for YWHAE-NUTM2B/E through FISH or real-time polymerase chain reaction and BCOR ITD through PCR. The results showed the identification of BCOR ITD in 9 of 22 ISTURCS (40.9%) and in 6 of 7 PMMTI cases (85.7%), and YWHAE-NUTM2B fusion is a rare event in ISTURCS . Santiago et al. confirmed BCOR ITD in five PMMTI cases through PCR and sequencing . Kao at el. showed that BCOR protein is diffused and positive in 13 out of 14 BCOR ITD positive tumors (92.9%), and all CCSK cases show strong and diffused nuclear BCOR immunoreactivity . BCL6 and BCOR proteins demonstrated diffused nuclear positivity in more than 90% of tumor cells in all five PMMTI cases, whereas they were negative in all CIFS cases . BCL6 is a molecular target of BCOR and is used as a confirmatory marker . Therefore, the expression levels of BCOR and BCL6 observed in PMMTI can serve as a useful marker.
ERMS occurs in the head, neck, and reproductive areas of infants and young children and should be distinguished from PMMTI. The microscopic characteristics of ERMS includes small round cells, oval or short spindle-shaped mesenchymal cells, and the stroma could be loosely myxoid zones. Positive myogenic IHC markers are evident in ERMS, whereas they are absent in PMMTI. ERMS has no specific molecular genetic changes.
EWS/PNET mainly occurs in the bone and extraskeletal sites. The prevalent age group is young people. It consists of primitive uniform small round cells and rarely shows myxoid changes. Special IHC markers are CD99, Fli1, and NKX2.2, and molecular genetic changes are EWSR1-FLI1 and EWSR1-ERG gene fusions [28, 29, 30].
Another article reported that PMMTI occasionally needs to be identified with undifferentiated myxoid lipoblastoma, but special PLAG1 rearrangement occurs in undifferentiated myxoid lipoblastoma .
H3K27me3 is highly expressed and associated with improved patient survival in multiple cancer [32,33]. Lu VM et al. Analyzed H3K27 trimethylation loss in malignant peripheral nerve sheath tumor (MPNST) through systematic review and meta-analysis. The results showed that the incidence of complete H3K27me3 loss is substantial in high-grade MPNST and is low in MPNST-mimics . In this case study, we found that the diffused nuclear expression of H3K27me3 may indicate improved prognosis for patients. This study is the first to investigate H3K27me3 expression in PMMTI.
ISTURCS is usually an exclusionary diagnosis, and its morphology occasionally overlaps with PMMTI and CCSK. However, several differences are found in IHC and molecular genetics.