Diagnostic Utility of BCL-1/Cyclin D1 Immunohistochemical Staining in the Evaluation of Hirschsprung Disease

Abstract

Hirschsprung disease (HD) is a disorder caused by the failed migration of neural crest cells, resulting in abnormal innervation of the colon. Histologic hallmarks include the absence of ganglion cells and the presence of hypertrophic nerve fibers. At present, an immunostain for calretinin is the most used ancillary study. The supportive staining pattern for HD is the absence of immunoreactive ganglion cells and mucosal nerve fibers (neurites). While studying a patient with mantle cell lymphoma involving the colon, we observed a similar immunoreactive pattern for ganglion cells and neurites with anti-BCL-1 and hypothesize that this immunostain might complement calretinin staining. To test this hypothesis, we prospectively collected biopsy and resection specimens from patients clinically suspected of having HD. BCL-1 immunoreactive ganglion cells and/or mucosal neurites were observed in 10 biopsy specimens of patients without HD while these elements were absent in biopsy and affected areas of resection specimens in 12 patients with HD. The staining of ganglion cells and neurites dependent of the source of the antibody used. The parallel negative staining of neural elements with 2 unrelated antibodies provides credence to the absence of immunoreactivity for calretinin in the diagnostic workup of patients suspected of having HD.

Keywords: BCL-1; Hirschsprung; Surg Path; ancillary tests; calretinin; immunohistochemistry.