Congenital Myenteric Hypoganglionosis

Abstract

Congenital myenteric hypoganglionosis is a rare developmental disorder characterized clinically by severe and persistent neonatal intestinal pseudoobstruction. The diagnosis is established by the prevalence of small myenteric ganglia composed of closely spaced ganglion cells with sparse surrounding neuropil. In practice, the diagnosis entails familiarity with the normal appearance of myenteric ganglia in young infants and the ability to confidently recognize significant deviations in ganglion size and morphology. We review clinical, histologic, and immunohistochemical findings from 12 patients with congenital myenteric hypoganglionosis in comparison with similar data from age-matched controls and clearly delineate the diagnostic features of the condition. Practical guidelines are provided to assist surgical pathologists, who are likely to encounter this condition only infrequently. The diagnosis typically requires full-thickness intestinal biopsy as the abnormality is confined to the myenteric plexus in many patients. Immunohistochemistry for Hu C/D may be used to confirm hypoganglionosis. Reduced staining for calretinin and NeuN implicates a selective deficiency of intrinsic primary afferent neurons in this disease.

A Novel Objective Pathologic Criterion for Isolated Hypoganglionosis

“…Previous reports have described mean values of the number of myenteric ganglion cells evaluated using HuC/HuD-immunostained sections in IHG cases as 23.3 and 30.1 ganglion cells per cm. 1,9 Our cutoff value of ≤ 18.7/cm was smaller than the abovementioned values and was considered reasonable as an abnormal decrease.…”

“…However, IHG is a rare disease, and only 3 studies, including the present one, have collected information from > 10 IHG cases. 1,9 Therefore, data from more IHG cases across multiple institutions are required for further validation. Second, an observer bias may have occurred in this study.…”

“…The quantified morphologic features were the number of myenteric ganglion cells (/cm), area of myenteric ganglia (µm 2 ), distance between myenteric ganglia (µm), and diameter of the nucleus of myenteric ganglion cells (µm); these features were reported in previous studies. 1,[7][8][9]13 Moreover, we counted the number of myenteric ganglia with an area > 2500 µm 2 (/cm) using an eyepiece micrometer (U-OCMSQ10/10, Olympus) (Supplementary Fig. 1, Supplemental Digital Content 1, http://links.lww.com/PAS/B818).…”

“…Isolated hypoganglionosis (IHG) is a rare congenital disease that typically presents with persistent symptoms of severe intestinal obstruction in the neonatal period 1–4 . These symptoms are nonspecific, and no imaging studies are useful for IHG diagnosis 5 .…”

“…1 and 2). 1,4,6–9 Due to these histologic features, IHG has also been reported as “ congenital myenteric hypoganglionosis.” 1 Although IHG exhibits such quantitative histologic findings, its quantitative pathologic criteria have not yet been established 2,9,10 …”