Compiled and organized: HadronsRarely, other small round cell sarcomas originating in the abdomen or gastrointestinal tract
Sarcoma with BCOR genetic changes is a mixture of spindle cells and round cells, and the specific genetic changes can be BCOR-related fusions or BCOR internal tandem duplications (BCOR-ITDs). Specifically, the tumors in this group included undifferentiated round cell sarcoma, primitive myxoid mesenchymal tumors of infancy (PMMTIs), and clear cell sarcoma of the kidney.
Sarcomas with BCOR::CCNb3 fusion are more common in bone than in soft tissue, with a ratio of 15:1；It is especially common in the limbs, pelvis, and spine, and rarely, the kidneys, lungs, and head and neck. The sarcoma of BCOR-ITD (also PMMTIs) occurs mainly in the soft tissues of the trunk, retroperitoneum, and head and neck. Round cell sarcoma with EWSR1-non-ETS fusion is a fusion of EWSR1 FUS with a non-ETS gene family member (mainly NFATC2 or PATz1). The morphology of this group of tumors is heterogeneous and rarely occurs in the abdominal cavity, usually in bone tissue with extraosseous involvement (NFATC2) or in soft tissues including retroperitoneal Nie (PATZ1).
Sclerosing epithelioid fibrosarcomaIt can originate in the abdomen, stomach, small intestine, cecum, pelvis, retroperitoneum, morphologically epithelioid cells, nest-shaped, and cord-like, with a sclerosing interstitium background. There is an overlap between the pathological morphology of the tumor and the molecular features of low-grade fibromyxoid sarcoma, which is a fibroblastic tumor with mild spindle ovoid cells located in the mucinous collagenous interstitium. Sclerosing epithelioid fibrosarcoma can be pure intrinsic or mixed with other forms; Most simple sclerosing epithelioid fibrosarcomas have rearrangements of EWSR1 and Creb3L1 Creb3L2, and occasionally FUS rearrangements. Diffuse expression of MUC4 occurs in 80-90% of cases; MUC4-negative sclerosing epithelioid fibrosarcoma has more extensive morphological changes with other fusions, such as YAP1::KMT2a or KMT2A::p RRX1.
Other small round cell tumors that occur in the pelvic, abdominal cavity, or gastrointestinal tract
Round cell epithelioid gastrointestinal stromal tumors:Epithelial-like morphology is seen in up to 25% of cases in gastrointestinal stromal tumors. SDH-deficient gastrointestinal stromal tumors are characterized by epithelioid and multinodular plexiform manifestations. Morphological manifestations of epithelioid gastrointestinal stromal tumors vary from large, polygonal, cytosolic eosinophilic cells to medium, and even small cells with high nucleoplasmic ratios, and in rare cases, small round cell tumors. PDGFRA-mutant gastrointestinal stromal tumors are generally epithelial, mainly in the stomach; Recently, PDGFRA immunohistochemistry has been found to be highly sensitive and moderately specific for this type of gastrointestinal stromal tumor.
High-grade (formerly known as round cell) myxoid liposarcoma:The tumor is characterized by fusion of FUS or EWSR1 with DDIT3 and occurs proximal to the extremities but can metastasize to the abdomen and retroperitoneum. The round-cell morphology of this tumor may resemble other round-cell sarcomas, such as Ewing sarcoma. When myxoid liposarcoma occurs in the abdominal cavity or retroperitoneum, metastases to typical sites should be excluded first.
CK-positive malignancy in the abdomen with EWSR1 fus::creb fusion:This is a newly recognized class of tumors that predominantly occur in the peritoneal cavity and have CK expression and EWSR1 fus::creb fusions. The morphology is a single morphological epithelioid cell with a multinodular distribution, and some phenotypes overlap with malignant mesothelioma, such as diffuse strong positive expression of AE1 AE3 and WT1, focal expression of CD34, but not expression of calretinin. Rarely, the shape is small oval cells with a cast-like nucleus, some of which resemble small cell carcinoma.
Epitheloid mesothelioma:Partial epithelioid mesothelioma in the thoracic cavity or peritoneum of young and middle-aged adults without a history of asbestos exposure has been reported in EWSR1 fus:ATF1 or EWSR1::YY1 fusions. The tumors in this group have a classic epithelial-like morphology, often solid nests or patches, with an unequal number of papillary or beam-like areas, and the interstitium is collagenous, seedless** or necrosis; Bap1 expression was still present in immunohistochemistry, suggesting a specific mesothelioma subtype. Because the epithelioid cells are monomorphic and located in the collagenous matrix, they may be mistaken for small round cell sarcoma.
Malignant peripheral nerve sheath tumor, small cell subtype:Malignant peripheral schwannomas in the abdominal cavity are well known, but small cell subtypes are rare. The morphology of these tumors is that the original neuroepithelial differentiation of round cells is flaky or nested, sometimes with aborted chrysanthemum-shaped masses. Small cell subtype malignant peripheral nerve schwannoma is distinguished from Ewing sarcoma by the absence of CD99 expression in the former, and the focal area will have more typical features of malignant peripheral schwannoma, such as alternating between cell-rich and sparse areas, or at least focal atypical.
Endometrial stromal sarcoma:Endometrial stromal sarcoma can occur in the pelvic and abdominal cavities**, sometimes at long intervals, and can be difficult to diagnose on needle aspiration biopsy. Low-grade endometrial stromal sarcomas may present as small, homogeneous cells with oval or round nuclei without atypical, sparse cytoplasm and a small amount of interstitium. It may be mistaken for a small round cell tumor, such as Ewing sarcoma; It is important to remember that middle-aged to older women have the possibility of endometrial stromal sarcoma and take care to combine it with relevant clinical history, such as hysterectomy and endometriosis.
From a differential diagnosis point of view, low-grade endometrial stromal sarcoma generally has a network of arterioles. In terms of immunohistochemistry, the tumor can express Desmin, SMA, H-caldesmon, broad-spectrum CK, WT1 and CD99, but CD10 is generally diffuse, strongly positive, and expresses ER, PR, and may express Cyclin D1 focially. In terms of molecular signatures, low-grade endometrial stromal sarcomas generally have a large number of fusions, most commonly JAZF1::SUZ12.
Figure 13Low-grade endometrial stromal sarcoma. Tumor cells are abundant, the cells are small and uniform round, distributed in patches, the nucleus is oval or round, no atypical, the cytoplasm is scarce, the interstitium is relatively small, and it is fibrous; A network of slender arterioles is also visible.
Neuroblastoma or Wilms tumor (Wilms tumor):Tumors in this group generally occur in very young patients, with neuroblastoma patients typically younger than 6 years of age and Wilms tumor typically younger than 10 years of age. There was no diffuse cell membrane staining of CD99 in this group of tumors.
Malignant rhabdomyomatoid tumors:Occasionally, tumors in this group are predominantly small round cell morphology with mild atypical rhabdomyocytes. The majority of tumors in this group occur in infants and children under 3 years of age, but extrarenal and extracranial cases can occur in **. Immunohistochemistry of SMARCB1 (INI1) nuclei is an intact cousin that can be used to distinguish it from other tumors.
takehome messages
Small round cell sarcoma is rare; For small round cell tumors in the pelvis or gastrointestinal tract, first attention should be paid to excluding cancer, lymphoma, and melanoma;
The diagnosis of small round cell sarcoma requires a combination of clinical and radiographic features, such as a history of the primary tumor and attention to previous histological sections;
Careful evaluation of the morphological lineage of certain specific diseases is required, as any interstitial or non-interstitial tumor may present with a small round cell morphology, at least focially;
Immunohistochemistry should pay attention to the use of sensitive markers, broad-spectrum lineage markers to exclude certain diseases, broad-spectrum CK such as AE1 AE3, broad-spectrum neural markers such as SOX10, broad-spectrum lymphohematopoietic markers should also pay attention to the addition of TDT to exclude acute lymphoblastic leukemia;
Because many small round cell sarcomas have a variety of immunophenotypes, the diagnosis needs to be made in combination with immunohistochemistry results (including focal positive and negative markers), histologic findings, and clinical features;
Pathologists need to be aware of the limitations of the molecular tests used, such as the detection of gene rearrangements or gene fusions, which are not specific.
End of Full Text: Previous Review: Practical Diagnostic Strategies for Small Round Cell Tumors of the Gastrointestinal and Abdominal Tracts (I).
Practical diagnostic strategies for small round cell tumors of the gastrointestinal tract and abdomen (2).