Yukihiro Noda

Autoimmune lymphoproliferative syndrome mimicking chronic active Epstein–Barr virus infection

Chronic active Epstein–Barr virus infection (CAEBV) is defined as a systemic EBV-associated lymphoproliferative disease characterized by fever, lymphadenopathy, and splenomegaly in apparently immunocompetent persons. Recent studies have revealed that EBV infects T or natural killer cells in most patients with CAEBV; the etiology of CAEBV, however, remains unknown. Autoimmune lymphoproliferative disorder (ALPS) is an inherited disorder associated with defects in apoptosis, and clinically characterized by lymphadenopathy, splenomegaly, hypergammaglobulinemia, and autoimmune disease. ALPS is most often associated with mutations in the FAS gene, which is an apoptosis-signaling receptor important for homeostasis of the immune system. Based on the clinical similarity between ALPS and CAEBV with respect to lymphoproliferation, we have examined the possibility of the co-occurrence of ALPS in patients with a diagnosis of CAEBV. In this study, we have identified FAS gene mutations in three Japanese patients with lymphadenopathy, hepatosplenomegaly, and unusual EBV infection, who were diagnosed with CAEBV. These observations, which indicate that the clinical development of ALPS may be associated with EBV infection, alert us to a potential diagnostic pitfall of CAEBV.

Postmortem Computed Tomography Imaging in the Investigation of Nontraumatic Death in Infants and Children

Objective. To determine the accuracy of postmortem computed tomography (PMCT) for the assessment of causes in nontraumatic deaths in children. Study Design. We enrolled cases of nontraumatic deaths of infants and children who underwent PMCT at a single center. The presumed cause of death determined by PMCT was prospectively compared with the clinical and pathological diagnoses of deaths. Results. Thirty-eight cases were enrolled for analysis. Among them, seven cases also underwent conventional medical autopsy. PMCT revealed an identifiable cause of death in accordance with the clinical diagnosis of death in 16 cases of the 38 cases (the concordance rate was 42%) and in accordance with the autopsy cause of death in four of the seven autopsy cases (the concordance rate was 57%). Among eight cases with unknown cause of death by clinical diagnosis, four cases (50%) were identified with cardiac tamponade as a cause of death (one case) and intracranial hemorrhage suggesting abuse (3 cases). Conclusions. PMCT seems to be a promising technique that might serve as a substitute for conventional medical autopsy and give us the complementary information to clinical diagnoses particularly in cases of child abuse. Larger multicenter trials are worthwhile to validate the general feasibility of PMCT.

A child with Epstein-Barr Virus-associated hemophagocytic lymphohistiocytosis complicated by coronary artery lesion mimicking Kawasaki disease.

There is considerable overlap between hemophagocytic lymphohistiocytosis (HLH) and Kawasaki disease (KD) in terms of aberrant immune response though the etiology of KD remains unknown. We present a case fulfilling the criteria of both HLH and KD complicated by coronary artery dilatation: HLH was confirmed to be triggered by Epstein-Barr virus. This case alarms us the possibility that even patients with HLH may be complicated by coronary artery lesion, which is one of the hallmarks of KD. We would like to draw attention that if features of KD become apparent in patients with HLH, echocardiographic examinations should be performed not to miss coronary artery lesion.

Alternating syndrome of inappropriate secretion of antidiuretic hormone and cerebral salt wasting in an infant with brain tumor.

dysmaturational/dysplastic process and are comprised of abnormally aggregated MPO-positive primary granules lacking sulfated glycoaminoglycans.2,3 In contrast, the lysosomal-origin granules of the inherited syndrome are MPO negative, as in our case. Similar granules have exceptionally been documented in ALL4,5 and the reasons behind their presence here are less clear. In our case, the restriction of these granules to the nonviable blast cells and an occasional one in continuity with the nucleus (Fig. 1D) made it very likely that they were simply a manifestation of nuclear degenerative changes and fragmentation rather than a true cellular product or accumulation. Rare lymphocytes that were present too showed prenecrotic changes (Fig. 1F), although this specific abnormality was restricted to the blasts. This unique “pathogenesis” has, to the best of our knowledge, not been considered before although biological artifacts mimicking Chediak Higashi inclusions are described.6 Silberman and colleagues reported Chediak Higashi-like giant intracytoplasmic inclusions in peripheral blood leukocytes of a child with a congenital hepatic vascular malformation complicated by disseminated intravascular coagulation and hemolysis. These were later ultrastructurally revealed to be phagocytosed schistocyte debris.6 The alternative possibility that our patient had the inherited Chediak Higashi syndrome and subsequently developed ALL might be speculated upon. An ALL-like morphologic picture may rarely develop during a florid Epstein Barr virus infection in these patients.7 This is, however, virtually impossible in our case due to the absence of any prior history or clinical stigmata of the syndrome (checked for retrospectively), the absence of the “granules” in residual lymphocytes in addition to the clear-cut expression of markers of immaturity (CD34 and TdT) on the surface of the B-lineage cells (blasts). To conclude, our finding of Chediak Higashi-like granules in degenerating lymphoblasts of a partially necrotic Ph-positive B-ALL adds to the spectrum of conditions that such curiosities may occur in. It also reminds us that quaint morphologic artifacts may lurk as pitfalls in myriad diagnostic settings. Deciphering them and calling their bluff often requires evaluation of all direct and indirect evidences available by the reporting haematopathologist. Prashant Sharma, MBBS, MD, DNB, DM Manorama Bhargava, MBBS, MD, FAMS Haematology Department, Superspeciality and Research Block, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, India (E-mail: sharma.prashant@pgimer.edu.in)

Long-term follow-up of a girl with primary aldosteronism: Effect of potassium supplement

We followed up a girl with primary aldosteronism for 8 y, which was diagnosed at 6 y of age when she was referred to us for evaluation of heart murmur and growth failure. The diagnosis of bilateral adrenal hyperplasia was made by selective adrenal venous sampling. Following potassium supplement, her retarded growth was corrected dramatically, and she attained a normal adult height. Puberty developed normally and menarche occurred at 12 y of age. Blood pressure was also controlled adequately. Myocardial hypertrophy associated with aortic damage was noted at 13 y of age. Chronic renal failure developed with proteinuria and enlarged renal cysts.