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The 22q11 deletion syndrome (22q11DS) is the most common microdeletion syndrome in humans and one of the chromosomal conditions most associated with psychosis and autism spectrum disorder. To date, only 2 neuropathologic studies of 22q11DS have been reported. Findings included polymicrogyria, neuronal heterotopias, excess subcortical white-matter (interstitial) neurons, significant white-matter gliosis/hypomyelination, and microvasculopathy. Here, we report on a 3-month-old infant with documented 22q11DS, tetralogy of Fallot, and pulmonary atresia. The brain exhibited tortuous cerebral vessels and proportionately smaller occipital lobes. Histologic examination revealed cerebral white-matter pathology and subtle differences in cortical lamination, including an excess of interstitial white-matter neurons compared with a sample of age-matched controls. There was a 15% increase in DARPP-32+ medium spiny neurons in the anterior-superior caudate. In this first neuropathologic report of an infant with 22q11DS, the findings were similar to previously reported manifestations and are likely secondary to perfusion issues, developmental microvasculopathy, and abnormal frontal cortical development.

The practice of central histopathologic review by expert pathologists has accompanied entry of patients onto multi-institutional therapeutic research protocols for the past half-century, and it is still a key component in the majority of therapeutic protocols conducted by the Children's Oncology Group (COG). Policies regarding pathology review have historically varied but have recently been standardized by the COG. Pretreatment central pathology review has been used to improve the accuracy of pathology data that is critical to the conduct of the study and to ensure that ineligible patients are not enrolled on a study. Pretreatment central review is unnecessary when there are established criteria for diagnosis, when institutions can uniformly apply these criteria, and when diagnoses are reliably reported. Pretreatment central review is appropriate when there are established diagnostic criteria and expert reviewers can consistently apply them but when institutional diagnoses show significant variability. It is inappropriate when there are no standard criteria or when variability exists among experts. Retrospective reviews (for example, those performed after protocol entry and treatment have occurred) historically have been used to verify institutional diagnoses and to record other features of tumors, prior to analysis of research questions. However, delayed reporting of discrepant diagnoses from retrospective reviews introduced obvious concerns regarding the appropriateness of treatment and exposed institutional pathologists and clinicians to significant professional risks. This article examines the historical usage and current status of the central pathology review process and the rationale and indications for its performance.

Morphologically, the distinction between undifferentiated embryonal sarcoma of the liver (UESL) and biliary tract rhabdomyosarcoma (RMS) can be uncertain because of some shared pathologic similarities. Patients with UESL have been consistently but erroneously enrolled in Children's Oncology Group (COG) treatment protocols because UESL was equated with RMS, despite the differing primary treatment modalities of these entities. Review of COG pathology files yielded 20 cases of UESL that were compared to 25 cases of biliary tract RMS. Clinicopathologic features including immunohistochemical staining were examined. In the UESL cases, the male:female ratio was 1:1 and the median age was 10.5 years. Histologically, hyaline globules and diffuse anaplasia were consistently present. The cases of RMS had a male:female ratio of 1.8:1 with a median age of 3.4 years and routinely lacked diffuse anaplasia and hyaline globules. Polyclonal desmin and muscle-specific actin were variably immunoreactive in UESL and RMS; however, myogenin and myogenic regulatory protein D1 (MyoD1) were uniformly negative in UESL and routinely positive in the majority of biliary tract RMS. Myogenin, in particular, was highly significant ( P = 0.0003) in distinguishing RMS from UESL. With a median follow-up of 8 months, 11 of 18 patients with UESL were still alive. The estimated 5-year survival for biliary tract RMS was 66%. Establishing the correct diagnosis of these distinct clinical and pathologic entities is important, as surgery alone may be curative in UESL, whereas initial chemotherapy is often recommended for the treatment of biliary tract RMS.