Niemann-Pick disease,type B with TRAP-positive storage cells and secondary sea blue histiocytosis |
| |
| Authors: | P Sharma R Kar S Dutta HP Pati R Saxena |
| |
| Institution: | Haematology Department, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India |
| |
| Abstract: | 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.Key words: Niemann pick disease, Gaucher disease, tartrate resistant acid phosphatase, sea blue histiocytosis.We present two unrelated patients who were referred to the Hematology OPD from Gastroenterology during work-up of long-standing splenomegaly 2 years apart and whose details are presented in | Open in a separate window
The marrow smears in both patients showed abundant classical Niemann Pick cells (foamy cytoplasm positive for the lipid stain Sudan black B, small central to eccentric nucleoli) with many sea-blue histiocytes, a well-recognized secondary phenomenon (Golde et al., 1975) ( and ). Diagnostic uncertainty arose when enzyme cytochemistry on the marrow smears showed intense tartrate resistant acid phosphatase (TRAP) activity in the foamy cells, periodic acid Schiff positive material and haemophagocytosis in the sea-blue histiocytes, findings hitherto described only in Gaucher cells (Weisberger et al., 2004) ( and ). No classical Gaucher cells were seen in multiple Romanowsky stained smears.Open in a separate windowThe bone marrow aspirate shows numerous Niemann Pick cells with abundant foamy cytoplasm and fewer and smaller sea-blue histiocytes (Jenner-Giemsa).Open in a separate windowThe multi-vacuolated Niemann Pick cells are positive for the lipid stain Sudan Black B. (Giemsa counterstaining).Open in a separate windowThe Niemann Pick cells variably measure 20–50 micrometers in greatest diameter. They are uniformly and intensely positive for tartrate resistant acid phosphatase. (Methyl green counterstaining). The sea blue histiocytes'' acid phosphatase is inhibited by tartaric acid (image not shown).Open in a separate windowThe Niemann Pick cells are only weakly positive for periodic acid Schiff stain. Gaucher cells would be expected to be brilliantly positive. (Haematoxylin counterstaining).
The diagnostic puzzle was resolved when both patients showed normal beta-glucocerebrosidase levels, very low levels of HDL cholesterol with low acid phosphatase, and in the one patient where it could be performed, a reduced but recordable level of sphingomyelinase activity (as seen in type B form), thus confirming clinico-pathologically the diagnosis of Niemann Pick disease, type B.A literature search reveals that although serum TRAP levels may be mildly elevated in patients with Niemann Pick disease, the enzyme has not been localized cytochemically to these cells previously (Chambers et al., 1977). Interestingly, a recent publication using sequence profiling and fold recognition methods suggests a remote evolutionary relationship between the phosphoesterase domain of acid sphingomyelinase (deficient in Niemann Pick disease) and purple acid phosphatases (mammalian form of which is TRAP) (Seto et al., 2004). The importance of this relationship is unclear but it is interesting to speculate whether there could be an upregulation of a related enzyme in face of congenital deficiency of acid sphingomyelinase in our cases.The iron content and the haemo-phagocytosis were possibly simply pointers towards the intrinsic histiocytic nature of the sea-blue histiocytes.The major lesson from these cases is to alert the pathologist to the possibility of TRAP and iron positive histiocytic and storage cells other than Gaucher cells that may display haemophagocytosis. This is especially relevant to avoid incorrect diagnosis in resource-restricted settings in India where specialized diagnostic tests may be inaccessible or omitted if the morphological and cytochemical findings are felt to be characteristic of Gaucher disease. |
