Compiled and organized: HadronsSmall round cell sarcomas that can originate in the abdomen or gastrointestinal tract are identified
CIC rearrangement sarcoma
It is an aggressive tumour with round and oval cell morphology that prefers in young** (median age 25-35 years) but has a broad age distribution (less than 25% of pediatric patients). Most occur in the deep soft tissues of the extremities or trunk, but can also occur retroperitoneally and in the pelvis. About 10% occur in internal organs, such as the gastrointestinal tract and kidneys. A small number (<5%) originate in bone tissue, which is different from Ewing sarcoma.
CIC rearrangement sarcoma is highly aggressive, has a high probability of metastasis, most commonly metastasizes to the lungs, and has a poor response to the Ewing sarcoma** regimen, with a significantly worse overall survival prognosis than Ewing sarcoma. The tumor had CIC rearrangements, and the most common fusion ligands were FOXO4, LeutX, NUTM2A, and NUTM1, and there was no histological difference between the different fusion ligands.
Histologically, the CRIC-rearranged sarcoma is distributed in patches of single cells, predominantly round, small to medium, often with a small number of epithelioid to spindle-shaped cells, and the background is fibromyxoid interstitium. Unlike Ewing sarcoma, CIC rearrangement sarcomas are at least focially mildly atypical and small nucleoli, with a small amount of dichrophilic or hyaline cytoplasm, nucleated**, and necrosis. The interstitium is usually focal and myxoid, which is also different from ewing sarcoma.
Figure 6The CRIC rearranged sarcoma has round, small to medium cells, similar to Ewing sarcoma.
Figure 7Sarcomas with CIC rearrangements, partly epithelioid cells with focal atypical and myxoid stromal, may also be spindle-shaped.
In terms of immunohistochemistry, the CRIC rearranged sarcoma CD99 was generally focal-positive, and a few cases were diffusely positive for the cell membrane. Most cases expressed ETV4 and WT1. The expression results of ERG, CD31 and Calretinin were different, and in rare cases, CK, S100 and myomorphic myogenous markers could be expressed. nkx2.2 Generally negative. Nut protein is expressed in CIC::NUTM1 rearranged sarcoma. CIC rearrangements can be detected by FISH, RT-PCR, or next-generation sequencing, but none of these techniques are particularly sensitive.
Figure 8Sarcoma of CIC rearrangement. Immunohistochemistry is nonspecific, CD99 is mostly focal positive (left), and ERG is diffuse nuclear positive, but this feature can also be seen in some Ewing sarcomas.
Poorly differentiated synovial sarcoma
This rarer form of synovial sarcoma is more common in older people and has a poor prognosis. Some cases have been reported in the abdomen, pelvis, retroperitoneum, and present as renal masses or hemorrhages, and may also be sporadic in the gastrointestinal tract and liver.
The morphology of poorly differentiated synovial sarcoma is generally cell-rich sheety, with round, hyperchromatic nuclei, sparse cytoplasm, basophilic, nuclear ** and necrosis visible. Up to 1 in 3 classic synovial sarcomas will have areas of poor differentiation. Poorly differentiated synovial sarcoma mimics other round cell tumors but rarely has large cell epithelioid manifestations and high-grade spindle cell morphology. The molecular definition of synovial sarcoma is the presence of a fusion of SS18 with one of several SSX genes (typically SSX1 or SSX2): in more than 90% of cases, there is a SS18::SSX1 SSX2 gene fusion that produces the SSX18-SSX fusion oncogene.
Figure 9Poorly differentiated synovial sarcoma is rich in cells, with a round nucleus and a sparse cytoplasm.
Figure 10In classic synovial sarcoma, there is often at least a focal area of poorly differentiated synovial sarcoma.
A poorly differentiated synovial sarcoma can very much resemble an ewing sarcoma. More than 90% of synovial sarcomas will express epithelial markers focially, and about 40% of poorly differentiated synovial sarcomas; The most common positive markers are AE1, AE3, or MNF116, CAM52. Sometimes the expression of high molecular weight CK can be seen; EMA is expressed in up to 95% of cases, and sometimes EMA is the only positive marker of epithelial differentiation.
Figure 11In synovial sarcoma, more than 90% of synovial sarcomas express epithelial markers to varying degrees (in this case, AE1 AE3).
Most cases express BCL-2, about 60% of cases express CD99 (generally cytoplasmic coloration), and about 40% express S100 locally. Rarely, desmin, sma, and h-caldesmon are also expressed. TLE1 is generally diffusely positive in more than 90% of cells, but its diagnostic specificity is limited, and spindle cell tumors involved in the differential diagnosis are also positively expressed. CD34 is almost always negative.
Ewing sarcoma of 1 3 expresses AE1 AE3 but not CK7, which has a positive rate of about 50% in poorly differentiated synovial sarcoma. Approximately 70% of Ewing sarcoma nuclei express FLI1, and poorly differentiated synovial sarcoma does not express this marker. Small round cell tumors generally do not express TLE1, which is also different from poorly differentiated synovial sarcoma. When tumors occur in the abdomen, it should be noted that focal cytoplasmic expression of CD117 can be seen in about 11% of monophasic synovial sarcomas and 8% of poorly differentiated synovial sarcomas. Rarely, there will be focal and weak positive expression of dog1 in synovial sarcoma. The recently studied SSX18-SSX fusion-specific antibody (E9X9V) was positive in 95% of synovial sarcomas but negative in morphologically similar lesions.
Rhabdomyosarcoma
For pelvic and abdominal lesions, rhabdomyosarcoma is mainly embryonal rhabdomyosarcoma, about 50% of which occur in the genitourinary tract, such as the bladder, prostate, cervix, parasoft tissues. Rarer sites include the abdominal cavity, retroperitoneum, biliary tract, liver, and kidneys.
Embryonal rhabdomyosarcoma is the most common type of rhabdomyosarcoma, occurring in about 1 to 3 patients under 5 years of age. Its morphology is heterogeneous, generally mildly to moderately atypical of primitive oval to spindle cells, arranged in bundles, against a background of mucinous collagenous interstitium, with varying degrees of rhabdomyoblast differentiation.
Figure 12Embryonal rhabdomyosarcoma with a morphological fascicle distribution of mild-to-moderate, primitive oval to spindle cells against a background of mucinous collagenous interstitium. If there is a predominance of densely packed round cells, it may resemble other small round cell sarcomas. More typical areas of embryonal rhabdomyosarcoma with fusiform findings and mucinoid interstitium may help confirm the diagnosis.
In terms of immunohistochemistry, the expression of desmin, myogenin and myod1 in embryonal rhabdomyosarcoma of varying degrees was mostly focal. There is no specific molecular test for this tumor: embryonal rhabdomyosarcoma has no specific fusion, is usually aneuploidy, and has multiple copy numbers (or entire chromosomes) acquired or missing. In general, there are changes in RAS family genes (HRAS, NRAS, KRAS) and changes in NF1, FGFR4, and PIK3CA.
Solid adenoalveolar rhabdomyosarcoma occurs in deep soft tissues, is uncommon in the abdominal cavity, and rare tumors around the pelvis or rectum can cause intestinal obstruction. The morphology is that the nucleus is round, centered, non-adherent, and the cells are solid sheets. Most solid adenoalveolar rhabdomyosarcomas have PAX3 or PAX7 fused with FOXO1.
To be continued
Previous review: Practical diagnostic strategies for small round cell tumors of the gastrointestinal tract and abdomen (1).