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.

[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.

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.

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.

Sea-blue histiocytosis secondary to Niemann-Pick disease type B: a case report.

Sea-blue histiocytosis is a morphological finding that can be associated both with acquired conditions of increased cellular turnover and inborn errors of lipid metabolism. We report a rare case of sea-blue histiocytosis associated with a mild phenotype of Niemann-Pick disease (NPD) type B in a 44-year-old man who presented with splenomegaly and mild thrombocytopenia. Diagnosis was guided by the morphological finding in bone marrow smears of foamy and sea-blue histiocytes and confirmed by the measurement of acid lysosomal sphingomyelinase activity below normal values. NPD type B is a rare inborn error of metabolism, with a benign course and prognosis, while types A and C are always associated with severe neurological involvement. In our patient diagnosis was confirmed by the specific enzyme assay of leukocytes (deficiency in sphingomyelinase activity). This is a simple and noninvasive method that is useful whenever clinical and morphological finding are relevant, and a primary hematological disorder has been ruled out.

Pulmonary involvement in Niemann-Pick disease: case report and literature review.

Niemann-Pick disease (NPD) is a rare, inherited, autosomal recessive, lipid storage disease. The pathognomonic intracellular accumulation of sphingomyelin results in the production and accumulation of 'foam cells'. Interstitial lung disease is a rare manifestation of NPD. We present the case of a 48-year-old white female with NPD involving the lungs, liver and spleen. The chest radiograph showed bilateral, predominantly basal reticulonodular infiltrates and serial pulmonary function tests over a period of years showed preserved expiratory airflow and a severely decreased diffusion capacity for carbon monoxide (DLCO). In view of her visceral involvement, lack of neurological symptoms and survival into adulthood, we believe our patient represents a case of type B NPD. In this type of NPD, aside from prominent hepatosplenomegaly and sexual immaturity, significant pulmonary infiltration with 'Pick cells' has been reported. To date, no therapeutic modality has been shown to alter the natural history of this disease, which results in progressive debilitation and death. This case is unique in that it provides the longest physiological follow-up in the literature, and provides data on the natural history of pulmonary involvement in NPD.

Sea-blue histiocyte syndrome in bone marrow secondary to total parenteral nutrition.

Clinical and hematological abnormalities can occur in patients receiving intravenous fat emulsions as part of a long-term parenteral nutrition; they consist of hepatosplenomegaly and peripheral blood cytopenia(s). These abnormalities lead to bone marrow examination which revealed numerous macrophages laden with blue staining pigment granules and separate lipid vacuoles, presenting the typical histochemical characteristics of sea-blue histiocytes. Thus, long-term parenteral nutrition including fat-emulsion sources may represent a further condition in addition to the wide variety of disorders which can be associated with sea-blue histiocytosis. Moreover, in view of its clinical and morphological presentation, this storage pathological state could be compared with the so-called sea-blue histiocyte syndrome described by Silverstein and colleagues.

Sea-blue histiocytosis and pancytopaenia associated with chronic total parenteral nutrition administration.

A 22-year-old female on chronic total parenteral nutrition for short bowel syndrome presented for investigation of pancytopaenia and hepatosplenomegaly. Bone marrow examination revealed an infiltrate of sea-blue histiocytes and cytochemistry confirmed these to be lipid laden macrophages. The total amount of fat in the feeding regimen was subsequently reduced, and there has been a partial haematological improvement. The occurrence of sea-blue histiocyte syndrome complicating the fat emulsion component of chronic total parenteral nutrition has been reported recently. To our knowledge this report is the first where reduction in the lipid content of the feeding regimem has resulted in an improvement in the degree of pancytopaenia.

Sea-blue histiocyte syndrome in bone marrow secondary to total parenteral nutrition including fat-emulsion sources: a clinicopathologic study of seven cases.

Bone marrow examination revealed a lipid-laden histiocytosis in seven patients undergoing long-term total parenteral nutrition necessitated by extensive short-bowel surgical resection. Clinical abnormalities occurred during this treatment which required bone marrow examination. These included hepatosplenomegaly and peripheral blood cytopenia; the median time to the detection of these abnormalities was 64 months. The most striking change within the bone marrow was the presence of many pigment-laden histiocytes which had the typical morphology of sea-blue histiocytes seen in the so-called idiopathic sea-blue histiocyte syndrome. The occurrence of sea-blue histiocytosis in the bone marrow in association with long-term parenteral nutrition for short-bowel syndrome has not, to our knowledge, been reported previously and should now be considered in the differential diagnosis of bone marrow sea-blue histiocytosis.

Sea blue histiocytosis: a common abnormality of the bone marrow in myelodysplastic syndromes.

AIMS: To determine whether myelodysplastic syndromes (MDS) are associated with sea blue histiocytosis in the bone marrow. METHODS: A retrospective review of bone marrow aspirates from 35 patients presenting consecutively with MDS and from 20 patients with each of the following: normal marrow appearance (routine staging for non-Hodgkin's lymphoma), polycythaemia rubra vera, immune thrombocytopenic purpura (ITP), chronic myeloid leukaemia (CML) in chronic phase. RESULTS: Sea blue histiocytes were present in the marrow in 12 of 35 cases of MDS and occurred in large numbers in three of these cases. Sea blue histiocytes varied in the degree of cytoplasmic granularity and some cells were intermediate in appearance between classic sea blue histiocytes and pseudo-Gaucher cells. Sea blue histiocyte granules additionally stained positively with Sudan black and periodic acid schiff. Sea blue histiocytes occurred only in the presence of marrow hypercellularity. Their presence did not correlate with FAB subtype, degree of dyserythropoeisis, or megakaryocyte numbers. No sea blue histiocytes were found in the normal marrow or polycythaemia cases. In ITP sea blue histiocytes were seen in two of 20 cases and in chronic myeloid leukaemia in eight of 20 cases. CONCLUSIONS: Sea blue histiocytes are a common cytological feature in the bone marrow of patients with MDS. As other disorders frequently associated with marrow sea blue histiocytes are relatively rare MDS is probably the most common cause of this phenomenon in a northern European population.

Sea-blue histiocytosis in a family with Niemann-Pick disease. A clinical, morphological and biochemical study.

Four siblings of a large Brazilian kindred are shown to have a variant of Niemann-Pick disease masquerading as the sea-blue histiocyte syndrome. They show a very similar clinical and laboratory picture: massive hepatosplenomegaly, low height for age, diffuse interstitial pulmonary infiltration, high levels of serum acid phosphatase and sea-blue histiocytes in the bone marrow. The neurological examination, as well as the retinae and maculae are normal. The high-density lipoprotein serum cholesterolemia ranged from 8.6 to 13.9 mg/dl, much lower than the 5th centile of normal distribution. The AI apolipoprotein concentrations in two siblings (0.29 and 0.44 g/l) were also below the minimal reference level of 0.90 g/l. The histochemical reactions demonstrated that sphingomyelin and ceroid are the accumulating substances in the marrow histiocytes. Electron microscopically, the cytoplasmatic granules of the histiocytes are phagolysosomes which contain scarce amorphous material, loose arranged lamellae, or dense well-organized structures with a fingerprint or fine network pattern. The sphingomyelinase activity in leucocyte extracts ranged from 4.9 to 8.6% and in cultured fibroblast extracts from 7.7 to 10% of simultaneous controls. The activity of other lysosomal enzymes was normal. Accordingly, this variant of Niemann-Pick disease should be classified as chronic nonneuronopathic sphingomyelinase-deficient type. The present data suggest that this variant is inherited as an autosomal recessive character. Our findings support the view that the sea-blue histiocyte syndrome is not an independent entity.

[Sea-blue histiocyte syndrome. Review of the literature apropos of a case of idiopathic splenomegaly in the adult]. / Le syndrome des histiocytes bleus. Revue de la littérature à propos d'une observation de splénomégalie idiopathique chez l'adulte.

A case of idiopathic splenomegaly with ceroid histiocytosis--the so-called sea-blue histiocytosis--is reported with reference to the literature. The histological, histochemical and ultrastructural features of stained sea-blue and ceroid-containing macrophages are described and their physiopathological significance is discussed. Attention is drawn to the distinctions, between idiopathic and secondary or associated forms, and the practical value of the pathological diagnosis is emphasized.