CDX2 is a homeobox domain-containing transcription factor that is important in the development and differentiation of the intestines. Based on recent studies, CDX2 expression is immunohistochemically detectable in normal colonic enterocytes and is retained in most, but not all, colorectal adenocarcinomas. CDX2 expression has also been documented in a subset of adenocarcinomas arising in the stomach, esophagus and ovary. In this study, we examined CDX2 expression in a series of large tissue microarrays representing 4652 samples of normal and neoplastic tissues. Strong nuclear staining for CDX2 was observed in 97.9% of 140 colonic adenomas, 85.7% of 1109 colonic adenocarcinomas overall and 81.8% of 55 mucinous variants. There was no significant difference in the staining of well-differentiated (96%) and moderately differentiated tumors (90.8%, P ¼ 0.18), but poorly differentiated tumors showed reduced overall expression (56.0%, Po0.000001). Correspondingly, there was an inverse correlation between CDX2 expression and tumor stage, with a significant decrease in staining between pT2 and pT3 tumors (95.8 vs 89.0%, Po0.012), and between pT3 and pT4 tumors (89.0 vs 79.8%, Po0.016). Analysis of 140 locally advanced, CDX2-positive colorectal adenocarcinomas coarrayed with their matching lymph node metastases revealed that expression of this marker was retained in 82.1% of the metastases. Consistent with previous reports, CDX2 staining was observed in gastric adenocarcinomas (n ¼ 71), more commonly in the intestinal-type than the diffuse-type (28.9 vs 11.5%, Po0.05). Occasional ovarian carcinomas were positive for CDX2, including mucinous (10.5%), endometrioid (9.3%) and serous variants (2%), but expression was either very rare or absent in primary carcinomas of the lung, breast, thyroid, pancreas, liver, gallbladder, kidney, endometrium and urinary bladder. A low frequency of CDX2 expression in pancreatic and biliary carcinomas observed on the microarrays was pursued further by comparing these tumors with ampullary adenocarcinomas on conventional sections. Ampullary adenocarcinomas were more commonly positive for CDX2 (19/24, 79%) than cholangiocarcinomas (1/11, 9%) and pancreatic carcinomas (3/20, 15%). In summary, CDX2 is a sensitive and specific marker for colorectal adenocarcinoma, although its expression is decreased among higher grade and stage tumors, and it is not invariably present in metastases from positive primaries. CDX2 may also be helpful in distinguishing adenocarcinomas of the ampulla from those arising in the pancreas and biliary tree.
This is the first evidence that lipopolysaccharide can precondition against cardiopulmonary bypass-related injury. Because lipopolysaccharide preconditioning is a systemic phenomenon offering proven protection against myocardial, hepatic, and pulmonary injury, this technique offers enormous potential for protecting against systemic neonatal injury related to cardiopulmonary bypass.
Ilioinguinal neuropathy is a well-described complication of mesh inguinal herniorrhaphy. We report the first human case, to our knowledge, of ilioinguinal nerve mesh entrapment with neuropathological changes that suggest an inflammatory cause for this chronic pain syndrome.
This case illustrates that the MRI findings for osteoblastoma can be misleading and caution should be used when evaluating benign tumors with known inflammatory responses on MRI. CT features seem to more accurately reflect the true nature and extent of the tumor.
The clinical, pathologic, and genetic findings of a boy with intranuclear nemaline rod myopathy are described. Serial muscle biopsies revealed myocyte nuclei containing inclusions that were immunoreactive for ␣-actinin and increased with age. Genetic analysis revealed a Val163Leu ACTA1 mutation previously associated with nemaline rod myopathy. Although initially delayed, he has reached all milestones and remains stable. These findings suggest intranuclear rods may increase with time and do not necessarily imply a poor prognosis. In this report, we describe a rare variant of NM characterized by the presence of inclusions exclusively in the nuclei with no sarcoplasmic deposits. To our knowledge, there are only two prior reports of this variant. 10,25 Examination of our patient's two biopsies revealed that the percentage of inclusions increased with age and, more important, that they were not necessarily a marker of a grave prognosis, as previously suggested. 2,9,19,20 CASE REPORTThe patient was delivered at 42 weeks gestational age by cesarean section for prolonged labor and cephalopelvic disproportion. At birth he weighed 7 lb 11 oz, had a weak cry, and was hypotonic. A computed tomography (CT) scan of the head revealed no abnormalities. Laboratory studies revealed an elevated serum creatine kinase (1,699 U/L; normal, 61-224 U/L). Neonatal blood screens for phenylalanine, leucine biotinidase, thyroxine, galactose, lactate, carnitine, very-long-chain fatty acids, amino acids, organic acids, and ammonia were unremarkable. Genetic tests for myotonic dystrophy, Prader-Willi syndrome, spinal muscular atrophy, and dystrophinopathy were negative. The patient's family history was negative; he has one younger brother, one younger sister, and one older sister, all of whom are unaffected. Physical examination on multiple occasions showed significant hypotonia, generalized muscle weakness, absent tendon reflexes, and pectus excavatum. A cardiac evaluation at 1 year of age was unremarkable. Developmental milestones were initially delayed, with speech and walking beginning at ϳ2 years of age. The patient is now ϳ9 years old, requires nocturnal oxygen support due to sleep hypoventilation, and has poor exercise tolerance (i.e., he is unable to ride a bicycle but does swim). Otherwise, he has been stable since ϳ4 years of age and is performing well in school, with good fine-motor, speech, auditory, and cognitive function.
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