PORTAL HYPERTENSION IN SYSTEMIC MASTOCYTOSIS

Portal hypertension in systemic mastocytosisPORTAL HYPERTENSION IN SYSTEMIC MASTOCYTOSIS
JEAN-PIERRE CAPRON, M.D., DIDIER LEBREC, M.D., CLAUDE DEGOTT, M.D., DOMINIQUE CHIVRAC, M.D., BRUNO COEVOET, M.D., AND JACQUES DELOBEL, M.D.
Clinique Mkdicale A, Laboratorie d’Ht+natologie, Centre Hospitalier Universitaire, Amiens, and the Unit6 de Recherches de Physiopathologie HPpatique (INSERM), Laboratoire Central d’Anatomie et Cytologie Pathologiques, H6pital Beaujon, Clichy, France
We report the case of a 66-year-old male patient with portal hypertension related to systemic mastocytosis. The liver was enlarged; microscopic examination showed portal mast cell infiltration and fibrosis. Portal hypertension was evidenced by splenomegaly, esophageal varices, and increased wedged-free hepatic venous pressure gradient. Arteriography showed that portal vein was patent. Portal hypertension could be the consequence of intrahepatic block due to mast cell infiltration and/or fibrosis of the liver.
Systemic mastocytosis is characterized by prolifera- tion of mast cells in skin, bones, lymph nodes, and parenchymal organs. l-3 Enlargement of the liver is present in nearly 70% of patients with systemic masto- cytosis.3 The hepatic lesions are represented by mild to moderate fibrosis in 13 to 38%, and mast cell prolifera- tion, as a diffise infiltrate or in well defined masses, in 38 to 57%.3,4 We report the case of a patient suffering from systemic mastocytosis with portal hypertension, a complication which has not been hitherto described in this disease.
Case Report In a 66-year-old non alcoholic man, systemic mastocytosis
was proved by typical skin changes (urticaria pigmentosa), generalized bone changes on roentgenograms (osteosclerosis and osteoporosis), mast cell infiltration of the skin, bone marrow, and gastric mucosa, and hyperhistaminuria (452 pg per 24 hr; normal, less than 50 pg per 24 hr) with normal fasting serum histamine (0.013 pg per ml; normal, 0.040 to 0.0090 pg per ml).
The liver was 17 cm on the midclavicular line; its surface was smooth and its consistance was firm. Splenomegaly was palpable 5 cm below the costal margin. Total serum bilirubin was 0.8 mg per 100 ml; serum alanine amino-transferase was 13 IU (normal, less than 15 U); serum alkaline phosphatase was 246 IU (normal, less than 170 U); 5’-nucleotidase was 25 IU (normal, less than 10 U); serum albumin was 4.5 g per 100 ml and y-globulin was 0.9 per 100 ml; prothrombin was 80% of normal; cholesterol was 0.18 g per 100 ml; fractional clearance of bromosulfophthalein was 0.138 min-’ (normal range, 0.110 to 0.160). Hepatitis B surface antigen was unde- tectable.
Clinical examination showed abdominal collateral circula- tion. No ascites was found. Endoscopy showed esophageal varices. Celiac and superior mesenteric angiography demon-
Received July 11, 1977. Accepted October 18, 1977. Address requests for reprints to: Dr. J. P. Capron, Clinique
Medicale A, Centre Hospitalier Universitaire, Place Victor Pauchet, 80030 Amiens CBdex, France.
The authors wish to thank Professor J. P. Benhamou for his advice and criticism during the preparation of this manuscript.
strated that the splenic and portal veins were patent. A hepatic vein catheterization was carried out with a radioo- paque catheter under fluoroscopic control: wedged and free hepatic venous pressures were 22 and 6 mm Hg, respectively; wedging was demonstrated by injection into the catheter of radioopaque dye. The gradient between wedged and free hepatic venous pressures was 16 mm Hg with normal range from 2 to 4 mm Hg.5 During this procedure, a transvenous liver biopsy was performed.” The liver specimen consisted of a tissue cylinder 2 cm long and 0.1 cm in diameter, which was placed in Bouin’s fixative. The portal tracts were enlarged with extensive fibrosis and abundant infiltration by polymor- phonuclear cells (fig. 1). The trabecular architecture remained normal. No liver cell necrosis was observed. A great number of mast cells were seen within portal areas and along the sinusoids. In fibrotic areas some lymphocytes and histiocytes were visualized. On hematoxylin and eosin stain, these cells appeared polygonal and smaller than hepatic cells. With Giemsa stain, mast cells contained intracytoplasmic deep blue granules. With metachromatic stains, such as toluidine blue, the granules were reddish blue (fig. 2).
Discussion In our patient the diagnosis of systemic mastocytosis
was established on the following arguments: urticaria pigmentosa, radiological osteocondensation and osteo- sclerosis, large numbers of mast cells in the skin, bone marrow, and gastric mucosa, and hyperhistaminuria.
Liver involvement is a frequent finding in systemic mastocytosis.3,4 Hepatomegaly, often associated with splenomegaly, is usually asymptomatic; however, as- cites has been described in some patients79 8 Liver function tests are usually normal even if the liver is markedly enlarged. However, in a few patients, in- creased alkaline phosphatase level and decreased bro- mosulfophthalein clearance have been reported.7* s, lo The hepatic cells are preserved and the architectural pattern of the liver is generally unaltered, although it may be distorted by a massive mast cell infiltrate.” A mild to moderate portal and periportal fibrosis is pres- ent in 13 to 38% of cases3* 4 Mast cells, which are absent or scanty in the parenchyma of the normal human
595
F 85).
‘IG. 1. Enlarged portal tract with extensive fibrosis and polymorphous cellular infiltration. Normal trabecular architecture (H & E 9X
live !r,l* are easily demonstrated by Giemsa staining in In our case portal hypertension is the consequence of the portal and periportal areas,13 or in the walls and/or intrahepatic block owing to mast cell infiltratioh Ol;
lun ien of the sinusoids,‘, I1 in the form of diffuse infil- fibrosis, or both. Dense cellular ifiltration of the porl Lal
tral te14 or well defined masses.8 areas, such as in cases of myeloproliferative SyndroI ne
FIG. 2. Numerous mast cells with intracytoplasmic reddish blue granules (arrows) (Toluidine blue, x 840).
March 1978 CASE REPORTS 597
or reticulosis, could be the cause of portal hypertension; however, in these cases, the gradient between wedged and free hepatic venous pressures is usually norma1.15 Portal hypertension is presumably secondary to portal fibrosis. High gradient between wedged and free hepatic venous pressures in the absence of regenerative nodules has been reported in several types of liver disease, such as primary biliary cirrhosis,16 congenital hepatic fibro- sis,” and liver schistosomiasis. l* Connective tissue stimulation and fibrosis are remarkable features of mast cell disease.” 2 A close relationship of the mast cell to the formation of the collagen fibrils has been suggested. The mast cell is known to participate in production or storage of pharmacologically active sub- stances such as heparin, histamine, and possibly hyalu- ronic acid. lg Addition of heparin to a solution of collagen results in the formation of collagen fibrils.20 Increased histamine synthesis is demonstrated in many tissues undergoing rapid growth or repair.” In systemic mas- tocytosis the heparin and the histamine contents in the liver are increased.*, l** 22 Our case suggests that mast cell disease would be another rare example of new fibre formation in the absence of liver cell necrosis.23
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Sweda JA, Abraham JP, Fine G, et al: Systemic mast cell disease. A review and report of three cases. Am J Med 32:227- 239, 1962 Demis DJ: The mastocytosis syndrome: clinical and biological studies. Ann Intern Med 59194-206, 1963 Sagher F, Even-Paz Z: Mastocytosis and the mast cell. Chicago, Year Book Medical Publishers Inc, 1967 Lennert K: Zur pathologischen Anatomie von Urticaria pigmen- tosa and Mastzellen-reticulose. Klin Wochenschr 40:61-72, 1962 Benhamou JP, Girond C, Guillemot R, et al: Etudes sur I’hemodynamique hepatique. VI. Pressions auriculaire droite, cave inferieure, sus-hepatique libre, sus-hepatique bloquee et intrasplenique au tours des cirrhoses. Rev Fr Etud Clin Biol 7:397-405, 1962
6. Lebrec D, Degott C, Rueff B, et al: Transvenous (transjugular)
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