Guidelines for synoptic reporting of surgery and pathology in Hirschsprung disease.

BACKGROUND/PURPOSE: Synoptic, or standardized, reporting of surgery and pathology reports has been widely adopted in surgical oncology. Patients with Hirschsprung disease may experience morbidity related to surgical factors or underlying pathology and often undergo multiple operations. Our aim is to improve the postoperative outcome and care of patients with Hirschsprung disease by proposing a standardized set of data that should be included in every surgery and pathology report. METHODS: Members of the American Pediatric Surgical Association Hirschsprung Disease Interest Group and experts in pediatric pathology of Hirschsprung disease participated in group discussions, performed literature review and arrived at expert consensus guidelines for surgery and pathology reporting. RESULTS: The importance of accurate operative and pathologic reports and the implications of inadequate documentation in patients with Hirschsprung disease are discussed and guidelines for standardizing these reports are provided. CONCLUSIONS: Adherence to the principles of reporting for operations and surgical pathology may improve outcomes for Hirschsprung disease patients and will facilitate identification of correlations among morphology, function, genetics and outcomes, which are required to improve the overall management of these patients. LEVEL OF EVIDENCE: V.

Enlarged and prominent nucleoli may be indicative of MYCN amplification: a study of neuroblastoma (Schwannian stroma-poor), undifferentiated/poorly differentiated subtype with high mitosis-karyorrhexis index.

BACKGROUND: According to the International Neuroblastoma Pathology Classification, neuroblastomas exhibiting MYCN amplification (A-MYCN) have unique histologic features-namely, undifferentiated/poorly differentiated subtype with a high mitosis-karyorrhexis index (U/PD-H). Nonetheless, certain tumors possessing these histologic characteristics contain a nonamplified MYCN gene (NA-MYCN). METHODS: The clinical characteristics of patients from the Children's Cancer Group (CCG) 3881 and 3891 studies who had neuroblastoma, U/PD-H, exhibiting A-MYCN (n=68) or NA-MYCN (n=33) were investigated. The histologic and cytologic features of tumors (A-MYCN, n=62; NA-MYCN, n=28) filed at the Pathology Reference Laboratory, Department of Pathology and Laboratory Medicine, Childrens Hospital Los Angeles, were reviewed, and nucleolar areas in undifferentiated neuroblastic cells were evaluated using image analysis methods. RESULTS: All 68 patients whose tumors exhibited A-MYCN had disease that was in an advanced clinical stage (Stage III or IV); 89.7% of these patients were diagnosed between ages 0.5 and 3.5 years, and 67 of the 68 had been treated with the high-risk protocol in the CCG-3891 study. Children whose tumors exhibited NA-MYCN were evenly distributed across all age groups; 30 of these 33 children had advanced-stage disease, and 26 had been treated with a high-risk protocol. The prognosis associated with A-MYCN (event free survival [EFS], 15.7%; overall survival [OS], 22.2%) was significantly poorer than the prognosis associated with NA-MYCN (EFS, 56.1%; OS, 69.3%). The lone histologic/cytologic difference between tumors exhibiting A-MYCN and tumors exhibiting NA-MYCN involved nucleolar appearance. Neuroblastic cells in tumors exhibiting A-MYCN were characterized by the presence of 1 or more large, prominent nucleoli, and the mean nucleolar area was significantly greater in the 18 tumors exhibiting A-MYCN that were assessed (7.63 microm2) than in the 16 tumors exhibiting NA-MYCN that were assessed (5.53 microm2; P=0.004). CONCLUSIONS: Neuroblastomas, U/PD-H, were found to vary in terms of molecular background and clinical behavior. The results of the current study indicate that nucleolar enlargement in neuroblastic cells may be a sign of MYCN amplification.

Intrapulmonary airways visualized by staining and clearing of whole-lung sections: the transparent human lung.

Methods for the study of cartilaginous airways represent technically very laborious and time-consuming procedures, many of these with the inevitable disruption or elimination of the distal bronchi and bronchioles. We describe and illustrate a methodology to demonstrate the cartilaginous support of the most distal intrapulmonary airways in hemisections or slabs of whole-, fixed-lung specimens. By this process, the cartilaginous framework of intrapulmonary air passages is highlighted and their outlines are defined. An important and distinct benefit of our procedure is the preservation of the alveolar parenchyma, vasculature and pleura, serving as an anatomic structural context. This improved methodology is based on procedures used in the past, now applied to entire half-sections or slabs of lungs, stained with toluidine blue, subsequent removal of stain from noncartilaginous elements and finally clearing of the specimen. The procedure takes 7-8 days but with limited technical - manual involvement. The resulting specimens demonstrate a highly complex, variable and at times, even unpredictable distribution of cartilage throughout the bronchial anatomy. This method represents a practical way of studying intact, this vital component of the respiratory tract. It also allows assessment of the potential implication of these critical smaller pathways in pathologic conditions, where thus far they have been under-studied.

Epstein-Barr virus-associated leiomyomatosis and posttransplant lymphoproliferative disorder in a child with severe combined immunodeficiency: case report and review of the literature.

The occurrence of smooth muscle neoplasms and lymphoproliferative disorders in immunocompromised patients is well recognized. We report the case of an 8-year-old girl with adenosine deaminase (ADA)-deficient severe combined immunodeficiency (SCID) status post-bone marrow transplant (BMT), in whom Epstein-Barr virus (EBV) was detected in innumerable leiomyomas involving the gallbladder (leiomyomatosis), and multifocal leiomyomas in liver, spleen, pancreas, intestinal tract, and lung. The leiomyomas of the gallbladder, liver, spleen, and lung were asymptomatic, while those located in the colon became clinically manifest by recurrent lower intestinal hemorrhage. The patient also developed extensive EBV-associated polymorphic lymphoproliferative disorder (PTLD) in nodal and extranodal sites. In addition, there were pulmonary and gastric adenovirus and small and large intestine cryptosporidum infections. Our case appears to be the first example of leiomyomatosis of the gallbladder coexisting with multifocal leiomyomas of the liver, spleen, pancreas, intestinal tract, and lung, as well as EBV-derived lymphoproliferative disorder in a young girl with ADA-deficient SCID. Awareness of the pattern of involvement and of the coexistence of benign leiomyomatous proliferations with lymphoproliferative disorder is of value when gallbladder, pancreatic, biliary tree, lung, and intestinal lesions become clinically manifest in these patients. The demonstration of EBV infection in both leiomyomata and the PTLD suggests a common pathogenesis that may have therapeutic and prognostic implications.