Mast cell leukemia with rapidly progressing portal hypertension

Abstract

Reported herein is an autopsy case of mast cell leukemia, a rare form of systemic mastocytosis, complicated with portal hypertension. A 52-year-old woman presented with urticaria-like skin symptoms, anemia, and thrombocytopenia. Atypical mast cells (CD2+, CD25+, CD117+) with toluidine blue metachromasia were found in the peripheral blood and on bone marrow aspiration smears. Chemotherapy with cytosine arabinoside and idarubicin was ineffective and the patient died of multi-organ failure with rapidly progressing hepatosplenomegaly and large-volume ascites 3 months after admission. At autopsy the bone marrow, spleen, liver, and lymph nodes were extensively infiltrated by atypical tumor cells with occasional bi- or multi-lobated nuclei. They were positive for mast cell tryptase and possessed an activating mutation of the c-kitgene (D816V). Ascites (2200 mL) and non-ruptured esophageal varices with submucosal hemorrhage indicated the presence of severe portal hypertension. Although there was no evidence of liver cirrhosis, the hepatic sinusoids were clogged with tumor cells, with a tendency to be more severe in the perivenular areas, and the lumens of central veins were obliterated by tumor cell infiltration. The present case demonstrates that non-cirrhotic portal hypertension due to blocking of sinusoidal and venous flow could be a serious complication in mast cell leukemia.

Systemic Mastocytosis and Mast Cell Tumors

“…A usually low-grade eosinophil component in the infiltrates is recognized, but this may be expected to be more significant in those cases of SM associated with hypereosinophilia (see above). Marked infiltration of the liver by abnormal cells of the mast cell lineage have also been reported for mast cell leukemia (Yoshida et al 2009) and aleukemic mast cell leukemia/ malignant mastocytosis . In mast cell leukemia, extramedullary leukemic infiltrates are most commonly found in the spleen, liver and lymph nodes (Valentini et al 2008).…”

“…Few informations are still available for liver pathology in case of SM-induced NCPH. NCPH can be caused by dense hepatic infiltrates in systemic mastocytosis (Capron et al 1978) or in mast cell leukemia (Yoshida et al 2009). In one case, liver biopsy disclosed dense fibrosis of hepatic arterial and portal venule walls, resulting in complete obstruction of some portal radicles, and focal fibrosis of outflow venules and peliosis were also present (Bonnet et al 1987).…”

“…Liver infiltration with abnormal cells can be massive and is then associated with marked infiltration of the bone marrow, spleen, and lymph nodes. At autopsy, the liver sinusoids, mainly in lobular zone 3, and central veins are clogged with mast cell tryptase-positive cells, causing rapidly progressive non-cirrhotic portal hypertension (Yoshida et al 2009). As in other organs, liver cells undergo damage induced by the neoplastic cells.…”

Primary Hepatic Vascular Neoplasms and Hematologic Neoplasms Affecting Liver Vessels

“…Affected portal spaces and sinusoids present with fibrosis deposit correlated with the amount of neoplastic mast-cells. Secondarily, a nodular regenerative hyperplasia with obliterative portal venopathy mimicking vascular portal-sinusoidal disease with clinically non-cirrhotic portal hypertension may develop [68,69].…”

The Lymphatic Headmaster of the Mast Cell-Related Splanchnic Inflammation in Portal Hypertension

“…This would explain why the functional endothelial cell-mast cell coupling plays the key role in the splanchnic inflammatory impairments induced by mechanotransduction in portal hypertension. In experimental and clinical portal hypertension, an increase of the splanchnic mast cells as well as the changes of their phenotype have been demonstrated [10,11,12]. The increase of the mast cells number in the hepato-intestinal axis when a pathological increase of portal hypertension is produced, suggests that portal hypertension is the cause of mastocytosis.…”