Pediatric autoimmune enteropathy: an entity frequently associated with immunodeficiency disorders.

The term pediatric autoimmune enteropathy was originally applied to a form of intractable diarrhea seen in children under the age of 6 months and characterized by male predominance, concurrent autoimmune-associated disorders, circulating gut autoantibodies, a lack of severe immunodeficiency and small bowel atrophy with prominent crypt apoptosis. However, recent studies have cast doubt over the specific clinicopathologic findings associated with this entity. We, therefore, collected 178 gastrointestinal biopsies from 14 patients and examined their clinical, serologic and pathologic findings. Patients at presentation ranged in age from birth to 15.9 years (median, 5.5 months; mean, 4.1 years) and included six males and eight females. All children suffered from chronic watery diarrhea and malnutrition. Concomitant-associated disorders were noted in 11 (79%) cases and included 10 (71%) with an immunodeficiency disorder and/or another autoimmune-related disease. Eleven patients (79%) were positive for anti-enterocyte antibodies. The salient findings of autoimmune enteropathy were most prominent in the small intestines and the majority (79%) of patients demonstrated villous blunting, crypt hyperplasia, mononuclear cell inflammatory expansion of the lamina propria and crypt apoptosis. The remaining (21%) patients showed marked intraepithelial lymphocytosis reminiscent of celiac disease. Further, acute cryptitis and crypt abscesses were seen in seven (50%) patients obscuring the presence of apoptosis. The absence of Paneth cells, goblet cells or both was noted in seven (50%) patients. Follow-up information was available for all patients with 13 (93%) receiving immunosuppressant therapy and demonstrating partial-to-complete response. In total, three patients died from continued diarrhea and sepsis with one decedent before treatment could be initiated. In summary, autoimmune enteropathy in children is a heterogenous disease with protean clinical and pathologic findings. Although anti-enterocyte antibodies were identified in the majority of the cases, their presence was variable and insensitive. In addition, pediatric autoimmune enteropathy was frequently encountered in the setting of immunodeficiency disorders.

Undifferentiated carcinoma of the esophagus: a clinicopathological study of 16 cases.

Undifferentiated carcinoma of the esophagus is a rare histologic variant of esophageal carcinoma. Using criteria based on studies of undifferentiated carcinomas arising at other sites, we have collected 16 cases of resected esophageal undifferentiated carcinomas. Patients ranged in age from 39 to 84 years (mean, 65.5 years) and were predominantly male (94%). The tumors were characterized by an expansile growth pattern of neoplastic cells organized in solid sheets and without significant glandular, squamous, or neuroendocrine differentiation. The neoplastic cells had a syncytial-like appearance, little intervening stroma, and patchy tumor necrosis. In a subset of cases, the tumor cells adopted a sarcomatoid (n = 2), rhabdoid (n = 1), or minor component (<5%) of glandular morphology (n = 3). In 1 case, reactive osteoclast-like giant cells were found interspersed among the neoplastic cells. Lymphovascular invasion, perineural invasion, and lymph node metastases were identified in 88%, 56%, and 81% of cases, respectively. In 12 (75%) specimens, the background esophageal mucosa was notable for Barrett esophagus. Consistent with the epithelial nature of these neoplasms, cytokeratin positivity was identified in all cases. In addition, SALL4 expression was present in 8 (67%) of 12 cases. Follow-up information was available for 15 (94%) of 16 patients, all of whom were deceased. Survival after surgery ranged from 1 to 50 months (mean, 11.9 months). Before death, 67% patients had documented locoregional recurrence and/or distant organ metastases. In summary, esophageal undifferentiated carcinomas are aggressive neoplasms and associated with a high incidence of recurrence and/or metastases and a dismal prognosis.