Sea-blue histiocytosis.

A 78-year-old woman with hypertrophic cardiomyopathy underwent a septal myomectomy and valve replacement. In the immediate postoperative period she developed shock of mixed etiology and died. At autopsy, hepatomegaly and splenomegaly were identified, with PAS and Giemsa positive intracellular ceroid granular deposits. Sea-blue histiocytosis is an extremely rare, chronic and benign deposit disease. It is characterized by hepatosplenomegaly, thrombocytopenia and lymphadenopathy. The presence of ceroid substance in granules in PAS and Giemsa stains should establish the diagnosis of suspicion.

Pancytopenia related to acquired sea-blue histiocytosis during chronic parenteral nutrition.

Bone marrow smear showing histiocytes (black arrow) containing sea blue granules stained with May-Grünwald Giemsa.

A progressive neurological condition with acquired sea-blue histiocytosis further the diagnosis of Niemann-Pick type C1 in a 10-year-old boy.

Sea-blue histiocytes in bone marrow can be associated with a number of conditions and have indeed often been reported in Niemann-Pick diseases, mostly in Niemann-Pick type B, but also Niemann-Pick type C. Rarely, it was reported to be related to a progressive neurological condition. In this work, early bone marrow aspirations in a boy following the discovery of hepatosplenomegaly at 1 month of age and later isolated splenomegaly did not reveal abnormal cells (which is not uncommon). Numerous sea-blue histiocytes were found in a repeated exam when the child was 10-year old, at a time he had developed a progressive neurological condition with frequent falls, clumsiness, slow and slurred speech, intellectual disability, dystonic movements, and dysphagia. Acquired sea-blue histiocytes should be considered initially on the basis of clinical symptoms. Whole-exome sequencing identified two variants in the NPC1 gene, leading to the diagnosis of Niemann-Pick type C1. This case points out the presence of sea-blue histiocytes in the bone marrow and has helped to reach a diagnosis of NPC1 which was very difficult to establish even after years of study. Given the rarity of this pathology and the variety of clinical presentations, it is important to communicate the possible forms of presentation of this syndrome.

A rare case of association between Budd-Chiari syndrome and sea-blue histiocytosis.

Budd-Chiari syndrome (BCS) is a rare disease characterized by obstruction of hepatic venous outflow tract with diversified etiologies. Sea-blue histiocytosis (SBH) is a kind of storage diseases defined by the deposition of abundant sea-blue histiocytes in various organs and can lead to hepatosplenomegaly, cirrhosis, or even liver failure. The association between BCS and SBH has never been reported before. Here, we report a patient with BCS presenting with hepatosplenomegaly, portal hypertension, and pancytopenia who was later confirmed to also have SBH.

Pulmonary involvement in sea-blue histiocytosis.

Sea-blue histiocytosis is one of the six types of Niemann-Pick disease. It is characterized by childhood onset of hepatosplenomegaly, lack of neurological involvement and diminished sphingomyelinase activity. Pulmonary system is rarely involved sea-blue histiocytosis. In this paper, we present a 39-years-old male who had previously diagnosed as sea-blue histiocytosis at the age of 15. He was admitted to our clinic due to productive cough, hemoptysis, fever and weight loss. His symptoms did not resolve with the antibiotic treatment and further investigations revealed pulmonary involvement of sea-blue histiocytosis. After diagnostic bronchoalveolar lavage, his symptoms were improved, interestingly. This rare entity was discussed with literature survey.

Niemann-Pick disease, type B with TRAP-positive storage cells and secondary sea blue histiocytosis.

We present 2 cases of Niemann Pick disease, type B with secondary sea-blue histiocytosis. Strikingly, in both cases the Pick cells were positive for tartrate resistant acid phosphatase, a finding hitherto described only in Gaucher cells. This report highlights the importance of this finding as a potential cytochemical diagnostic pitfall in the diagnosis of Niemann Pick disease.

[Sea-blue histiocyte syndrome associated with home parenteral nutrition]. / Síndrome del histiocito azul marino en relación a nutrición parenteral domiciliaria.

A case of a 55 years-old male with long-term Crohn's disease without response to medical treatment and many intestinal fistula is presented. After the last bowel resection, home parenteral nutrition was started. He presented chronic hepatopathy and pancytopaenia. After 9 months of home parenteral nutrition hepatic function and pancytopaenia began to deteriorate. Bone marrow examination revealed an infiltrate of sea-blue histiocytes. He made unsatisfactory progress and died due to a multiorganic failure.

Splenomegaly with sea-blue histiocytosis, dyslipidemia, and nephropathy in a patient with lecithin-cholesterol acyltransferase deficiency: a clinicopathologic correlation.

A 31-year-old man with no significant medical history presented with a 5-day history of progressive left upper quadrant abdominal pain. Physical examination revealed a tender guarded abdomen, no icterus, and bilateral corneal "arcus senilis"-like changes. Laboratory workup showed a mild normocytic, normochromic anemia; and target cells were seen in the peripheral blood smear. Serum was turbid; and the lipid profile showed elevated total cholesterol, low high-density lipoprotein cholesterol, and elevated triglycerides. Urinalysis revealed nephrotic range proteinuria with microhematuria. An abdominal computed tomographic scan demonstrated a homogeneously enlarged spleen. The patient was discharged after symptomatic treatment to be followed as an ambulatory patient. Several days later, he returned with severe left upper quadrant pain and was admitted to the surgical service for further evaluation. A splenectomy was performed for a suspected splenic lymphoma. Upon gross examination, spleen was moderately enlarged, weighing 780 g. Sectioning revealed a beefy red cut surface without gross lesions. Wright-Giemsa-stained touch imprints showed many sea-blue histiocytes. A renal biopsy was also performed, demonstrating focal segmental glomerular sclerosis and mesangial expansion with extramembranous and intramembranous deposition of lipids. In the absence of hematologic malignancy and in light of the abnormal lipid profile, a disorder of lipid metabolism was suspected. Histologic and ultrastructural findings in the kidney and spleen raised the likelihood of lecithin-cholesterol acyltransferase (LCAT) deficiency, which was confirmed by the markedly decreased serum LCAT activity and serum LCAT mass. We describe a case with the triad of splenomegaly with sea-blue histiocytes, nephropathy, and dyslipidemia in a patient with LCAT deficiency.

Síndrome del histiocito azul marino en relación a nutrición parenteral domiciliaria / Sea-blue histiocyte syndrome associated with home parenteral nutrition

Presentamos un caso de un varón de 55 años con Enfermedad de Crohn de larga evolución con mala respuesta al tratamiento médico y múltiples fístulas al que se le inició nutrición parenteral domiciliaria (NPD) tras su última resección intestinal. Presentaba hepatopatía crónica no filiada y pancitopenia leve. Tras 9 meses de soporte nutricional parenteral se produce un empeoramiento de la función hepática y la pancitopenia. Se realizó biopsia de médula ósea que mostró histiocitos azul marino. La evolución fue tórpida falleciendo a consecuencia de un fallo multiorgánico (AU)

A case of a 55 years-old male with long-term Crohn's disease without response to medical treatment and many intestinal fistula is presented. After the last bowel resection, home parenteral nutrition was started. He presented chronic hepatopathy and pancytopaenia. After 9 months of home parenteral nutrition hepatic function and pancytopaenia began to deteriorate. Bone marrow examination revealed an infiltrate of sea-blue histiocytes. He made insatisfactory progress and died due to a multiorganic failure (AU)

[A case of a Korean adult affected by type B Niemann-Pick disease: secondary sea-blue histiocytosis and molecular characterization].

Niemann-Pick disease (NPD) is an inherited metabolic disorder caused by a deficiency of the enzyme acid sphingomyelinase coded by SMPD1 gene. In contrast with type A NPD, a severe neurodegenerative disease of infancy, type B NPD patients have little or no neurodegeneration, and frequently survive into adulthood. Although over 100 mutations have been found within the SMPD1 gene causing NPD, there was only one report about SMPD1 mutation status of a Korean NPD patient. We report a case of a 32-yr-old female, who presented with thrombocytopenia without any neurologic involvement. Hepatosplenomegaly was detected by both physical examination and imaging studies, and a thoracic radiograph examination showed a pattern of interstitial lung disease. Biochemical tests revealed increased liver enzymes, cholesterol, triglyceride, and LDL-cholesterol, and decreased HDL-cholesterol. Sea-blue or foamy vacuolated histiocytes occurred in bone marrow and liver. Sequencing analysis of SMPD1 using genomic DNA from peripheral leukocytes identified a compound heterozygote of two mutations at exon 2: p.E246K and p.A357V. The former is a known mutation in an Italian patient, and the latter has not been reported yet. She has received oral rosuvastatin to treat hyperlipidemia at a dose of 10 mg per day for 4 months. This is the second report in which the mutation of SMPD1 gene was detected in a Korean NPD patient. The active genetic analysis of SMPD1 gene in patients with typical findings of type B NPD would enable us to facilitate diagnosis as well as to accumulate data on molecular characteristics of Korean NPD patients.

A Case of a Korean Adult Affected by Type B Niemann-Pick Disease: Secondary Sea-blue Histiocytosis and Molecular Characterization / 대한진단검사의학회지

Niemann-Pick disease (NPD) is an inherited metabolic disorder caused by a deficiency of the enzyme acid sphingomyelinase coded by SMPD1 gene. In contrast with type A NPD, a severe neurodegenerative disease of infancy, type B NPD patients have little or no neurodegeneration, and frequently survive into adulthood. Although over 100 mutations have been found within the SMPD1 gene causing NPD, there was only one report about SMPD1 mutation status of a Korean NPD patient. We report a case of a 32-yr-old female, who presented with thrombocytopenia without any neurologic involvement. Hepatosplenomegaly was detected by both physical examination and imaging studies, and a thoracic radiograph examination showed a pattern of interstitial lung disease. Biochemical tests revealed increased liver enzymes, cholesterol, triglyceride, and LDL-cholesterol, and decreased HDL-cholesterol. Sea-blue or foamy vacuolated histiocytes occurred in bone marrow and liver. Sequencing analysis of SMPD1 using genomic DNA from peripheral leukocytes identified a compound heterozygote of two mutations at exon 2: p.E246K and p.A357V. The former is a known mutation in an Italian patient, and the latter has not been reported yet. She has received oral rosuvastatin to treat hyperlipidemia at a dose of 10 mg per day for 4 months. This is the second report in which the mutation of SMPD1 gene was detected in a Korean NPD patient. The active genetic analysis of SMPD1 gene in patients with typical findings of type B NPD would enable us to facilitate diagnosis as well as to accumulate data on molecular characteristics of Korean NPD patients.

Secondary sea-blue histiocytosis derived from Niemann-Pick disease.

Sea-blue histiocytosis is a rare disorder seen in patients with lipid metabolic or ceroid storage diseases. Sea-blue histiocytes are ceroid-laden macrophages detectable by May-Giemsa staining. We report a case of a 28-year-old woman diagnosed with Niemann-Pick disease at 2 or 3 years of age. To confirm this diagnosis, we examined her bone marrow, which revealed scattered foci containing aggregates of foamy macrophages. May-Giemsa staining identified blue-staining foamy macrophages, referred to as sea-blue histiocytes. In summary, we report the detection of sea-blue histiocytosis in an adult with Niemann-Pick disease.

Aggressive histiocytic disorders that can involve the skin.

Histiocytoses are a heterogeneous group of disorders that are characterized by the proliferation and accumulation of reactive or neoplastic histiocytes. Three classes of histiocytoses have been defined: class I, Langerhans cell disease; class II, non-Langerhans cell histiocytic disease without features of malignancy; and class III, malignant histiocytic disorders. Although the disorders in classes I and II usually have a benign appearance on histology and are commonly non-aggressive and self-healing, some can cause debilitating or even fatal outcomes. Such cases beg the question: what stimulates aggressive behavior of a classically benign disease? New molecular information may now provide insight into the driving force behind many of the aggressive histiocytoses. In this article, we review Langerhans cell disease and seven aggressive histiocytoses that can involve skin, discuss histologic features that may forecast a poor prognosis, and discuss the molecular findings that help to explain the pathophysiology of these aggressive histiocytic disorders.

Variable expressivity of the clinical and biochemical phenotype associated with the apolipoprotein E p.Leu149del mutation.

Splenomegaly with sea-blue histiocytes, thrombocytopenia and hypertriglyceridemia is a very rare association that has been described in only one report to date. The molecular defect in the two reported patients consists in a deletion of a leucine at position 149 in the receptor-binding region of the apoE molecule. Here, we report on another family in whom the proband and his brother were diagnosed with splenomegaly, thrombocytopenia and hypertriglyceridemia. An apoE p.Leu149del mutation was found in both subjects. A large beta band in the VLDL fraction and elevated VLDL cholesterol-to-plasma triglyceride ratio was observed in the proband only. Their mother, presenting with isolated hypertriglyceridemia, also carried the same p.Leu149del mutation. The coexistence of factors facilitating the development of hypertriglyceridemia and/or low HDL-cholesterol level could explain why the proband and his brother developed a splenomegaly with thrombocytopenia, whereas the mother did not. Moreover, the presence of an apoE2 allele in the proband likely explains the more severe phenotype we observed in this subject. In conclusion, the apoE p.Leu149del mutation results in a very striking phenotype including one or all symptoms among splenomegaly, thrombocytopenia and hypertriglyceridemia, and should be considered as a differential diagnosis of storage disorders in the causes of splenomegaly with sea-blue histiocytes.

Acquired sea-blue histiocytosis in beta thalassemia major.

Primary sea-blue histiocytosis is a rare syndrome. Secondary or acquired sea-blue histiocytosis occurs in a wide array of hematologic and systemic disorders, rarely these cells have been found in cases of thalassemia. A case of sea-blue histiocytosis in a patient of thalassemia is being reported for its rarity.