Mild changes of hepatic nodular regenerative hyperplasia may cause portal hypertension and be visible on reticulin but not hematoxylin and eosin staining

Nodular regenerative hyperplasia (NRH) can manifest as alternating parenchymal compression/expansion on hematoxylin and eosin (H&E) staining and as reticulin collapse/nodularity on reticulin staining. Histologic diagnosis can be challenging, especially when there is mild disease and on limited biopsy samples. We reviewed clinical and histologic parameters in a large series of NRH. We identified 60 liver specimens convincingly showing changes of NRH and reviewed them for clinical (age, sex, symptoms, lab values, portal hypertension [PHTN], NRH etiology) and histologic (inflammation, sinusoidal dilation, cholestasis, architectural change, portal vascular abnormalities, degree of changes on reticulin) parameters. The cases came from 28 women and 32 men (median age: 54 years). Most (55, 92%) were biopsies. Thirty patients were symptomatic. Forty-five cases showed mild NRH changes on reticulin; 24 of these (53%) showed them on H&E as well. Fifteen demonstrated well-developed changes on reticulin, which were always seen on H&E as well. Sinusoidal dilation was commonly observed in both of these subgroups (88% overall). Portal vascular abnormalities were seen in 33%. Well-developed NRH was diffuse more often than mild NRH (53% vs. 4%, P < 0.0001). Twenty-nine patients had clinically confirmed or likely PHTN. Of these, 21 showed mild and 8 showed well-developed NRH changes; only 3 had concomitant advanced fibrosis. Chemotherapy was the most frequent known cause of NRH; 30 patients lacked any definite etiology. NRH can be difficult to diagnose on biopsy, particularly since mild changes may be visible on reticulin but not H&E; even these patients can have PHTN. Additionally, NRH is often idiopathic, potentially lowering clinical and pathologic suspicion. Pathologists should have a low threshold for ordering reticulin stains, especially when a patient is known to have PHTN. Sinusoidal dilation, while nonspecific, commonly accompanies NRH.