Slavisa Djuricic

Recombinase‐activating gene 1 immunodeficiency: different immunological phenotypes in three siblings

We report different immunological phenotypes in three siblings from consanguineous family with recombinase‐activating gene 1 (RAG1) gene mutations. Null mutations of RAG genes result in severe combined immunodeficiency (SCID) with absent T and B cells. Hypomorphic mutations with retained activity of RAG genes may lead to a ‘leaky’ SCID with some features of Omenn syndrome (OS) or typical OS. In our three patients, homozygous, hypomorphic RAG1 gene mutation (g.368–369delAA) was detected. Two patients presented with T−B−SCID phenotype while the youngest patient developed T+B+NK+SCID phenotype with expansion of autologous T‐cell receptor (TCR) γδ‐positive T cells, increased immunoglobulin levels and retained ability for antibody production. Similar to originally reported patients with this newly recognized immune phenotype, our patient developed disseminated cytomegalovirus (CMV) infection and autoimmune cytopenia.

Pre-operative Differentiation of Pediatric Ovarian Tumors: Morphological Scoring System and Tumor Markers

OBJECTIVE To investigate the importance of morphological scoring systems in differentiation of ovarian tumors in childhood. METHODS Morphological assessment using DePriests index was performed for all patients with histopathological confirmation of ovarian tumor, with evaluation of tumor markers, from January 1997. RESULTS Fifty-three girls (age range 13 months to 19 years) were surgically treated for 59 ovarian tumors, including six bilateral. All lesions with cystic appearance on ultrasonography were benign, 23 of 35 semisolid, and four of ten solid tumors were also benign. Stage of malignant disease was as follows: stage I, ten; stage II, two; stage III, six. Sensitivity, positive predictive value and accuracy by DePriests and Uelands indexes for benign tumors (score <7) were: 0.88, 0.79; 0.89; and 0.94, 0.84; 0.93; respectively. Elevated levels of tumor markers were observed in 17 patients, including four patients with endocrine manifestations. In 24 patients ovaries were successfully preserved, including two patients with foci of immature teratoma in a dermoid cyst. CONCLUSION Ultrasonographic assessment with morphological analysis recommended by DePriest and Ueland is a very useful procedure for differentiating benign from malignant ovarian tumors in children. Tumor markers and endocrinological investigation are also useful for preoperative evaluation.

Successful treatment of hodgkin lymphoma in nijmegen breakage syndrome.

Nijmegen breakage syndrome (NBS) is a rare DNA repair disorder characterized by microcephaly, immunodeficiency, and predisposition to malignancy. We report on a 5-year-old patient with NBS who presented with nodular sclerosing type of Hodgkin disease stage IVB. Chemotherapy consisting of COPP/ABV regimen with reduction at 75% of full doses was employed. During this treatment, no major toxic or infectious complications were observed. Complete remission was achieved lasting now for 20 months. In DNA repair disorders, prognosis of Hodgkin disease is poor as opposed to excellent overall prognosis in general pediatric population. Better survival may be achieved both with adopted, disease-specific regimens, and individualized approach considering patients clinical condition. Also, better recognition and treatment of infections during chemotherapy may reduce early deaths in patients with DNA repair disorders.

Propionibacterium propionicus Infection in Chronic Granulomatous Disease

Correspondence Propionibacterium propionicus Infection in Chronic Granulomatous Disease Sir—Bourdeaut et al. [1] recently described 2 pediatric patients with chronic granulomatous disease (CGD) who developed chest infections caused by Pro-pionibacterium acnes. We describe a 7-year-old boy with CGD who developed a Propionibacterium propionicus infection. CGD is an inherited disease caused by defects in superoxyde-generating nicotin-amide adenine dinucleotide phosphate oxidase of phagocytes [2]. Impairment of oxygen-dependent intracellular killing mechanisms results in severe infections with catalase-producing Staphylococcus aureus, Burkholderia cepacia, or Aspergil-lus species [3]. In our patient, CGD was diagnosed at 3 months of age after an episode of sup-purative cervical lymphadenitis. X-linked inheritance of CGD was supported by the finding of intermediate values with the ni-troblue-tetrazolium (NBT) test (47% of neutrophils were NBT positive) of a blood sample from the patients mother. He was given prophylactic cotrimoxazole; he was free of major infections. At 7 years of age, he was admitted to our institute because of chest-wall contusion. At admission he was febrile (temperature, 39ЊC) and tach-ydispneic (respiration rate, 50 breaths/ min). Laboratory values were as follows: erythrocyte sedimentation rate, 84 mm/h; hemoglobin, 147 g/L; WBC count, 52.0 ϫ 10 9 cells/L, with 45.2 ϫ 10 9 neutro-phils/L; C-reactive protein, 237 mg/L (normal range, !10 mg/L). Chest radiography revealed a left-side pleural effu-sion. A thoracic CT scan showed microab-scesses of the left lower lobe. Chest drainage yielded 300 mL of fibrinous ex-udate. Empirical antibiotic treatment with tobramycin and ceftazidime was started. The patient became afebrile 48 h later but pleural effusion persisted, and a thoracot-omy was perfomed 2 weeks later. Pathological examination of the lung tissue specimen revealed microabscesses and granulomatous inflammation. Results of staining for mycobacteria and fungi were negative. Direct Gram staining of pleural fluid and lung biopsy specimens revealed non–acid-fast, gram-positive filamentous rods identified as P. propionicum. Isolates were sensitive to penicillin, cephalospo-rins, and vancomycin. We continued treatment with penicillin, and complete clinical remission was achieved 1 month later. The most common causes of pneu-monitis in patients with CGD are Aspergillus and Nocardia species and Burkholderia cepacia [3]. However, various opportunistic, catalase-producing microbes may infect patients with CGD [2, 3]. P. propionicus is a less common caus-ative agent of a disease similar to actino-mycosis [4]. Thoracic actinomycosis results from aspiration of pieces of infectious material from the teeth and may involve the chest wall, the lungs, or both. Intact mucosa are the first line of defense, because P. propionicus, …

Nasopharyngeal Capillary Arteriovenous Malformation with Ancient/Symplastic Change: A Simulator of Malignancy

There are only 8 published cases of symplastic hemangioma (SH), a relatively recently described, distinct benign entity characterized by pleomorphic vascular smooth muscle and interstitial cells in a pre-existing, long-standing vascular lesion. Seven of these cases were of SH in cutaneous locations, and 1 case was described in the mediastinum. We report the case of the 12-year-old girl with a nasopharyngeal tumor mass with prominent symplastic changes arising in the background of a combined capillary arteriovenous malformation. After critical analysis of all published cases of SH, it is clear that these lesions commonly represent capillary arteriovenous malformations (CAVM) with ancient/symplastic changes according to current terminology proposed in the classification required by the International Society for the Study of Vascular Anomalies (ISSVA). This is the first such lesion reported in a mucosal location and presenting in the pediatric age group. CAVM with ancient/symplastic change follows a benign clinical course, but it can simulate a malignant vascular tumor.

Appendiceal involvement in a patient with Gaucher disease

Almost any anatomical compartment may be involved in Gaucher disease (GD). Abdominal lymphadenopathy occurred during enzyme replacement therapy in more than a dozen children with GD so far. A fourteen-year-old boy from Serbia developed clinical signs of acute appendicitis six years after the onset of GD type 3 related abdominal lymphadenopathy. Ultrasound examination showed diffuse thickening of the intestinal wall in the ileocoecal region with periappendicular infiltration. An appendectomy was performed four months after conservative treatment with antibiotics. Histopathology revealed macrophages with cytological characteristics of Gaucher cells densely crammed in mesoappendiceal adipose tissue. Also the multifocal replacement of subserosal tissue by Gaucher cells and their infiltration to a variable depth of muscularis propria of the appendix were verified. Frank infiltration of the vermiform appendix with Gaucher cells represents a novel observation in a wide spectrum of manifestations reported in GD. A possible causative relationship of this infiltration with appendicitis is considered.

Aggressive human neuroblastomas show a massive increase in the numbers of autophagic vacuoles and damaged mitochondria.

ABSTRACT Autophagy is activated in cancer cells in response to multiple stresses and has been demonstrated to promote tumor cell survival and drug resistance in neuroblastoma (NB). This study was conducted to analyze the ultrastructural features of peripheral neuroblastic tumors (pNTs) and identify the relation of the types of NTs, the proliferation rate, and MYCN gene amplification with a number of autophagic vacuoles. Our results indicate that aggressive human NBs show a massive increase in the number of autophagic vacuoles associated with proliferation rate and that alteration of the mitochondria might be an important factor for the induction of autophagy in NTs.