How skin and liver can lead to diagnosis

A 73-year-old woman was referred by her hematologist for cholestasis of unknown origin. She was recently diagnosed with chronic myelomonocytic leukemia grade 0 in a context of fatigue, night sweats, weight loss and monocytosis. A PET-CT showed hepatosplenomegaly and multiple centimetric adenopathy. The diagnosis was confirmed by a bone marrow aspiration and biopsy. The evolution of the patient is marked by the appearance of cholestasis and an erythematous firm skin nodule of the right forearm. The skin lesion was biopsied to rule out a cutaneous localization of the patient’s known hemopathy. Histology showed an infiltration of the dermis with a population of immature cells. The immunohistochemical analysis of those cells showed positive CD117 and CD4 staining leading to the diagnosis of a skin localization of the chronic myelomonocytic leukemia. Given the persistence of cholestasis (alkaline phosphatases 737 IU/L and gamma glutamine transferase 119 IU/L), a transvenous liver biopsy was performed. Hepatic venous pressure gradient was 10 mmHg. Histology revealed a cellular infiltration of the portal tracts. The immunohistochemical analysis showed massive liver infiltration of CD117 and CD25 positive cells. Ductular proliferation with ductular damage, neutrophilic inflammatory infiltrate and dissecting fibrosis of the portal spaces was also present. What’s your diagnosis? Many diseases can affect the liver and skin, such as hemopathies (lymphoma, histocyotosis, systemic mastocytosis), systemic diseases (sarcoidosis, inflammatory bowel diseases, vasculitis), autoimmune diseases (lupus erythematous, systemic sclerosis, Sjögren syndrome). The presence of clusters of abnormal reactive and neoplastic mast cells with positive immunohistochemical staining for CD117 and CD25 in the liver is compatible with a systemic mastocytosis with an associated hematologic neoplasm (SM-AHN). When skin and bone marrow histology were revised (after liver histology), CD25 immunohistochemistry showed multifocal CD25 positive clusters of abnormal mast cells. Serum tryptase was elevated at 192,0 microg/L. KITD816V mutation was present. Treatment with midostaurine was started. She was non-responder and a second line therapy with avapritinib (in compassionate use) was started leading to the normalization of liver tests. The patient is still alive, after 2 years of follow up. Systemic mastocytosis is an infiltration of different organs by mast cells. Liver damage is common and can present as hepatomegaly, disturbance of liver enzymology, portal hypertension or hepatocellular insufficiency. Histology may show an infiltration of the portal spaces or sinusoids, cholestasis, cholangitis, focal nodular hyperplasia, septal and peri-sinusoidal fibrosis, veno-occlusive disease and secondary extramedullary hematopoiesis.