Unusual diffuse liver fibrosis accompanying transient myeloproliferative disorder in Down's syndrome: a report of four autopsy cases and proposal of a hypothesis

Abstract

Transient myeloproliferative disorder (TMD), an acute leukemia-like disorder in neonates with Down's syndrome, is characterized by spontaneous regression of abnormal blast growth. Because proliferating blasts frequently express phenotypes of megakaryocytic lineage and, as a result, this disorder resembles acute megakaryoblastic leukemia (AMKL), it would be of interest to determine whether myelofibrosis, a common complication of AMKL, is also present in TMD. Pathologic observations of four autopsy cases of TMD showed that myelofibrosis was not present in any of them, whereas intralobular diffuse liver fibrosis was present in all of them. Laboratory data of four additional cases showed hepatic dysfunction in all of them, suggesting a close association between hepatic lesions and TMD. From these results, we propose a hypothesis that the abnormal blasts with megakaryocytic properties in TMD originate from the fetal liver and cause liver fibrosis, as AMKL cells are thought to cause myelofibrosis by producing collagen-stimulating cytokines in the bone marrow. This hypothesis also seems to explain some other unique aspects of TMD.

Platelet‐derived growth factor may be associated with fibrosis in a Down syndrome patient with transient myeloproliferative disorder

“…Down syndrome with TMD is sometimes associated with liver fibrosis, which usually takes a lethal course (2)(3)(4).…”

The Management of Neoplastic Disorders of Haematopoeisis in Children with Down's Syndrome

“…It may be the cause of stillbirth in DS. In one series of eight patients with the complication, two were long-term survivors (Miyauchi et al, 1992). Infants may die of fulminant liver failure while the TMD is regressing.…”

“…Extensive myelofibrosis and generalized visceral fibrosis are occasionally present (Becroft & Zwi, 1990;Zipursky et al, 1992). Miyauchi et al (1992) offered an interesting theory: the signs and symptoms of hepatic fibrosis may dominate TMD because the leukaemic blasts arise from fetal hepatic blood-forming cells. Normally, the transition from hepatic to medullary myelopoiesis accompanies the regression of TMD.…”

Guidelines for the investigation and management of Transient Leukaemia of Down Syndrome

“…Massive hepatomegaly (beyond the umbilicus) was almost completely confined to the high-risk group. Miyauchi et al (1992) reported a series of 8 cases of TL-DS, of whom 6 died due to hepatic disease. In those who died, mean conjugated bilirubin at presentation was 84 lmol/l (42-122), progressing to a mean of 319 lmol/l (158-400) at the time of death.…”