Six cases are reported of an osteoclast-rich tumor of the gastrointestinal tract that should be segregated from GIST. Five of the cases were located in the small bowel and one in the stomach. The age of the patients ranged from 13 to 37 years. The tumors behaved aggressively, with metastases to regional lymph nodes, liver, and other intra-abdominal sites. Microscopically, the tumor cells were medium-sized, predominantly oval, relatively monomorphic, diffusely immunoreactive for S-100-protein, and negative for CD117, CD34, HMB-45, and Mart-1. They were admixed with scattered osteoclast-like, multinucleated giant cells which were S-100-protein negative and KP1-positive. One case studied cytogenetically had the karyotype 46XX t(12;22)(q13;q12). The cases here reported are interpreted as examples of a distinctive type of gastrointestinal neoplasm which shares some features with clear cell sarcoma of soft parts (melanoma of soft parts), including in one case the chromosomal translocation that is characteristically associated with that entity.

The clinical, histologic, immunophenotypic, ultrastructural, and molecular features of a distinctive gastrointestinal tumor are described. Sixteen patients, 8 women and 8 men aged 17 to 77 years (mean age, 42 y; 63% less than 40 y) presented with abdominal pain, intestinal obstruction, and an abdominal mass. Mean tumor size was 5.2 cm (range, 2.4 to 15.0 cm). The tumors arose in the small bowel (10), stomach (4), and colon (2) and were histologically characterized by a sheet-like or nested population of epithelioid or oval-to-spindle cells with small nucleoli and scattered mitoses. Five cases showed focal clearing of the cytoplasm. Scattered osteoclast-type multinucleated giant cells were present in 8 cases. The tumor cells were positive for S-100 protein, SOX10, and vimentin in 100% of cases, for CD56 in 70%, for synaptophysin in 56%, for NB84 in 50%, for NSE in 45%, and for neurofilament protein in 14% of cases. All cases tested were negative for specific melanocytic, gastrointestinal stromal tumors, epithelial, and myoid markers. Ultrastructural examination of 5 cases showed features of primitive neuroectodermal cells with clear secretory vesicles, dense-core granules, occasional gap junctions, and no evidence of melanogenesis. EWSR1 gene rearrangement was assessed by fluorescence in situ hybridization in 14 cases. Twelve cases (86%) showed split EWSR1 signal consistent with a chromosomal translocation involving EWSR1. One case showed extra intact signals, indicating that the nuclei possessed either extra copies of the EWSR1 gene or chromosome 22 polysomy. Only 1 case showed no involvement of the EWSR1 gene. Six cases demonstrated rearrangement of the partner fusion gene ATF1 (46%), and 3 showed rearrangement of CREB1 (23%); 2 cases lacked rearrangement of either partner gene. Clinical follow-up was available in 12 patients and ranged from 1.5 to 106 months. Six patients died of their tumors (mean survival, 32 mo; 83% less than 24 mo). At last follow-up, 4 patients were alive with regional, lymph node, and liver metastases, and 2 patients were alive with no evidence of disease. The tumor described here is an aggressive form of neuroectodermal tumor that should be separated from other primitive epithelioid and spindle cell tumors of the gastrointestinal tract. The distinctive ultrastructural features and absence of melanocytic differentiation serve to separate them from soft tissue clear cell sarcomas involving the gastrointestinal tract. The designation "malignant gastrointestinal neuroectodermal tumor" is proposed for this tumor type.

Total parenteral nutrition (TPN)-induced liver injury is a common complication in neonates managed with newborn intensive care. In several of these cases, irreversible and even fatal liver damage may develop, with patients dying of liver failure. In spite of multiple studies over several years, the pathogenesis of TPN-induced liver damage remains poorly understood. Clinical data from 24 neonates with clinical history of receiving TPN who died at Yale-New Haven Children's Hospital and had autopsies performed, were collected by medical record review without knowledge of liver pathology findings. Liver histological sections from these patients were evaluated for multiple parameters without knowledge of the clinical course. Continuous data were analyzed by Wilcoxon signed-rank test and Mann-Whitney test, and dichotomous data by Fisher's exact test; P < 0.05 was considered significant. Different histopathological abnormalities with varying degrees of severity were observed. A progression in the severity of histopathological changes in relation to duration of TPN administration (DTPN) was found. While patients with DTPN of < 2 wk had no fibrosis or only mild degrees of fibrosis, patients with more than 6 wk of DTPN developed moderate-to-severe fibrosis. Similar results were observed for cholestasis and bile duct proliferation. We did not find significant differences for birth weight, gestational age, occurrence of necrotizing enterocolitis, sepsis, or enteral feedings between the group with normal-to-mild liver changes ( n = 16), and the group with moderate-to-severe liver changes ( n = 8). On the other hand, DTPN was significantly different between these two groups ( P = 0.008). Also, patients small for gestational age ( P = 0.003) and patients with bronchopulmonary dysplasia ( P = 0.001) were more commonly seen in the group with moderate-to-severe histopathological findings. Intracellular copper was detected in 12.5% of patients with moderate-to-severe liver changes, and was found in 50% of patients with normal-to-mild liver findings ( P = 0.04). Detection of copper from tissue sections also decreased with DTPN, being observed in 57% of patients with < 2 wk DTPN and in none of the patients with > 12 wk DTPN. Our findings confirm the known significant relationship between the duration of TPN and liver injury. While previously described associations with birth weight, gestational age, enteral feedings, necrotizing enterocolitis, and sepsis were not noted, our study suggests that poor intrauterine growth may be a significant clinical risk factor for TPN-induced liver injury. In addition, our findings suggest that copper may have a protective effect against the development of TPN-induced liver damage.

Prolonged exposure to infection appears to influence fetal/neonatal development. We characterize the relationship between histologic patterns of inflammation and microorganism recovery from the placentas of live born infants delivered before the 28th postmenstrual week. The subamniotic parenchyma of 835 placentas delivered by cesarean section were cultured and evaluated for specific histologic patterns of inflammation in a blinded fashion. Cases with prolonged membrane rupture were excluded. Microorganisms were recovered from 41% of placentas. Microorganisms found more frequently in placentas with high-grade chorionic plate inflammation include Actinomyces, Prevotella bivia, Corynebacterium sp., Escherichia coli, Peptostreptococcus magnus, multiple species of Streptococci, and Mycoplasma sp., including Ureaplasma urealyticum. These microorganisms were also associated with fetal vasculitis (neutrophilic infiltration of chorionic plate stem vessels or umbilical cord). Recovery of microorganisms from placental parenchyma is associated with histologic inflammation. The same microorganisms responsible for inciting high-grade chorionic plate inflammation are also most likely to promote fetal inflammation.

This study population is unique in its size and recruitment by gestational age rather than birth weight. Inflammation occurred frequently, but not in placentas that had characteristics of vasculopathy. The prevalence of inflammation decreased with increasing gestational age, while vasculopathy increased. Funisitis need not be accompanied by chorionic inflammation.