Hyperganglionosis in Pneumatosis Cystoides Intestinalis- A Clinicopathological Review in Adults

Purpose/Background: Pneumatosis cystoides intestinalis, a rare entity, is not an isolated diagnosis but a finding that suggests an underlying process whose pathogenesis is not well understood. In this case series, we explore a novel histopathological finding of hyperganglionosis in pneumatosis cystoides intestinalis [PCI] as a cause-vs-effect phenomenon. Methods: In a previously published index case of PCI we discovered hyperganglionosis as an associated finding. This discovery led to a twenty-year retrospective search of the Laboratory Information Service [LIS] in our surgical pathology laboratory that identified a total of twenty three cases with reported finding of PCI of which seven cases were excluded due to lack of availability of histological slides and /or blocks. In the remaining sixteen cases all the relevant histopathological slides were reviewed to confirm the diagnosis of PCI. One representative block in each case was subjected to immunohistochemical staining with antibodies to S100, Calretinin and CD68 for further evaluation of hyperganglionosis with review to their clinical context. Results: This study reports on sixteen cases of PCI that have been studied in detail with their additional stains and their clinicopathological review. All cases upon review confirmed the presence of the diagnostic pathological finding of multiple, varied size and shapes of non-communicating cysts of PCI either mucosal/ submucosal intramuscular and/or subserosal. Additionally, prominent, enlarged hypertrophic ganglions associated with hypertrophic nerve fibers were seen in association with these cysts as highlighted by S100 and Calretinin. CD68 stained slides outlined the histiocytes and giant cells surrounding the cysts of PCI as expected. Conclusion: The exact pathogenesis of non-communicating air-filled cysts within the bowel wall remains poorly understood especially in cases with no evidence of perforation /obstruction and /or ischemic changes/. Many theories have been proposed to explain the presence of intramural gas that include the mechanical theory of mucosal injury, bacterial theory of gas production, counterperfusion-saturation theory and the pulmonary gas theory. We propose a neuronal theory with a detailed discussion of dysgenetic ganglion cells with abnormal peristalsis resulting reversal airflow’ with intramural accumulation of intraluminal air or that these hypertrophied ganglions and nerves could be the resultant effect of the forced intramural expansion by the cysts; thus, reminiscent of the debate of which came first -the chicken or the egg.