The incidence, mortality and timing of Pneumocystis jiroveci pneumonia after hematopoietic cell transplantation: a CIBMTR analysis.

Pneumocystis jiroveci pneumonia (PJP) is associated with high morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Little is known about PJP infections after HSCT because of the rarity of disease given routine prophylaxis. We report the results of a Center for International Blood and Marrow Transplant Research study evaluating the incidence, timing, prophylaxis agents, risk factors and mortality of PJP after autologous (auto) and allogeneic (allo) HSCT. Between 1995 and 2005, 0.63% allo recipients and 0.28% auto recipients of first HSCT developed PJP. Cases occurred as early as 30 days to beyond a year after allo HSCT. A nested case cohort analysis with supplemental data (n=68 allo cases, n=111 allo controls) revealed that risk factors for PJP infection included lymphopenia and mismatch after HSCT. After allo or auto HSCT, overall survival was significantly poorer among cases vs controls (P=0.0004). After controlling for significant variables, the proportional hazards model revealed that PJP cases were 6.87 times more likely to die vs matched controls (P<0.0001). We conclude PJP infection is rare after HSCT but is associated with high mortality. Factors associated with GVHD and with poor immune reconstitution are among the risk factors for PJP and suggest that protracted prophylaxis for PJP in high-risk HSCT recipients may improve outcomes.

Griscelli syndrome: rare neonatal syndrome of recurrent hemophagocytosis.

Griscelli syndrome (GS) is a rare inherited disease characterized by immunodeficiency and partial albinism. The microscopic findings of the skin and hair are highly suggestive of the disease. The GS locus colocalizes on chromosome 15q21 with the myosin-Va gene (MYO5a), and mutations have been identified in few patients. We describe a 2-month-old Hispanic girl with severe pancytopenia secondary to hemophagocytosis. Even though a mutation at the Griscelli locus had not been identified, her clinical features and outcome were typical of GS. The purpose of this article is to alert physicians to the association between GS and hemophagocytosis. We suggest that GS should be considered in infants with hemophagocytosis because the features of partial albinism can be subtle. The relevant literature is summarized.

Bone marrow transplantation in patients with Fanconi anemia: experience with cyclophosphamide and total body irradiation conditioning regimen.

Eleven patients with Fanconi anemia (FA) underwent bone marrow transplantation (BMT) between March 1985 and May 1990 in a single institution. Ten patients received bone marrow from healthy full human leukocyte antigen (HLA) matched siblings and one patient from her father (one antigen mismatch). Ten patients were conditioned with cyclophosphamide (Cy) at a dose of 5 mg/kg per day for 4 days followed by total body irradiation (TBI) for a total of 600 cGy over 3 days. Six of the 11 patients are alive and have normal reconstitution of their bone marrow. Median follow-up was 72 months (range 42-84). Three of the 10 patients who received Cy and TBI (two HLA compatible, one antigen mismatch) had graft failure. Five patients developed at least grade III acute graft-versus-host disease (GVHD). The rates of graft failure and GVHD are, however, still significantly high. Modification of the conditioning regimen and GVHD prophylaxis is needed to improve the outcome.

Imaging and compartmental classification of solid pelvic tumours in children.

Thirty-five children aged from 1 day to 16 years (median 5 years) with solid pelvic tumours were investigated with US, CT and MR. All three methods gave similar estimates of tumour size. For defining location of the tumours, the pelvis was divided into three midline compartments (anterior, middle and posterior) and a right and left lateral compartment. CT and MR were accurate and equally reliable in determining the tumour location, US was less accurate. Evaluation of confinement to organ of origin was uncertain, regardless of imaging modality. Tissue characteristics with CT and MR did not contribute to the differentiation of the various tumour types, and contrast medium enhancement did not improve the discrimination. Compartmental localization was equally well assessed by CT and MR and, together with sex, was found to correlate with the tumour type.

Imaging of solid kidney tumours in children.

Eighteen children aged 6 months to 12 years with 20 solid renal tumours: 13 Wilms' tumours (WT), 2 clear cell sarcomas of the kidney, 1 malignant rhabdoid tumour of the kidney and 2 cases of bilateral nephroblastomatosis with Wilms' tumour underwent evaluation with US, CT and MR imaging. Contrast-enhanced CT and non-enhanced MR were equally accurate in determining the size and origin of the tumour but were unreliable in separation of stages I, II and III. US could only accurately assess the size of the tumours. MR characteristics varied somewhat between WTs and non-WTs but contrast-enhanced MR imaging might be useful for separation of WTs from nephroblastomatosis.

Focal xanthogranulomatous pyelonephritis in a young child.

An 18-month-old female child presented with fever and an abdominal mass, which, after ultrasonography, computed tomography, and magnetic resonance imaging was considered to be an atypical cystic renal neoplasm. Nephrectomy was performed. Histopathological examination demonstrated the mass to be focal xanthogranulomatous pyelonephritis. This lesion should be considered in the differential diagnosis of renal neoplasms in childhood, particularly cystic Wilms' tumor or Wilms' tumor with significant intratumoral hemorrhage.

Fine-needle aspiration biopsy diagnosis of extrarenal malignant rhabdoid tumor.

Two cases of extrarenal malignant rhabdoid tumors are presented in which diagnosis was suggested by fine-needle aspiration biopsy and confirmed by histologic and electron microscopic examination. Fine-needle aspiration smears in both cases revealed round to polygonal cells with vesicular nuclei and prominent nucleoli. Several tumor cells contained cytoplasmic inclusions composed of intermediate filaments. A majority of the tumor cells stained strongly for vimentin and cytokeratin. Electron microscopic examination revealed many cells with large aggregates of intermediate filaments corresponding to the cytoplasmic inclusions. Fine-needle aspiration biopsy may be used for diagnosing malignant rhabdoid tumor. The diagnosis may be further confirmed by immunohistochemistry and electron microscopy.

Fine-needle aspiration biopsy of Langerhans histiocytosis (histiocytosis-X).

A series of 14 fine-needle aspiration biopsies (FNAB) from histologically proven cases of histiocytosis-x (Hx) were reviewed. The smears revealed a variable mixture of Langerhans cells, eosinophils, macrophages, polymorphonuclear cells, and giant cells. Based on the predominant cells present, the cases were further categorized as Langerhans cell predominant (nine cases), eosinophil predominant (two cases), and macrophage predominant (three cases). Langerhans cells were usually polygonal without significant evidence of phagocytosis and frequently contained indented nuclei. In three cases, several Langerhans cells showed prominent dendritic processes. Electron microscopy in 10 cases revealed Langerhans cells with varying degrees of morphologic differentiation. All cases studied revealed Birbeck granules. These findings indicate that FNAB may be an effective technique for diagnosing Hx.

Cellular radiosensitivity of patients with different types of neurofibromatosis.

Skin fibroblast cell strains were developed from nine Saudi patients with different types of neurofibromatosis (NF) and nine healthy subjects (controls), and their radiosensitivity was compared following chronic exposure to gamma-radiation at a dose rate of 0.0076 Gy/min (1 Gy = 100 rads). Cells from both normal appearing skin and café-au-lait spots of the different NF patients (7 out of 9) clearly showed increased radiosensitivity, with D10 (dose resulting in 10% survival) values of 2.0-4.4 Gy for the former and 3.0-4.8 Gy for the latter, compared to the normal controls (with D10 values of 6.1-10.6 Gy). These data provide further evidence of an association of enhanced cellular sensitivity to chronic irradiation with NF regardless of the classes they belong to. Hypersensitivity to specific carcinogens may, thus, be a factor responsible for the increased propensity to cancer in these patients.

Fine-needle aspiration biopsy diagnosis of rhabdomyosarcoma: cytologic, histologic, and ultrastructural correlations.

A series of 15 cases of rhabdomyosarcoma diagnosed by fine-needle aspiration biopsy (FNAB) and confirmed by histopathology is reviewed. Cytologically, the tumors were composed of a variable mixture of cells, which according to the degree of differentiation were categorized as early, intermediate, or late rhabdomyoblasts. Histologically, the tumors were divided into embryonal 9, monomorphic round cell 4, and alveolar rhabdomyosarcoma 2. Comparison of histological and cytological features revealed that embryonal types were composed mainly of early rhabdomyoblasts. Recognition of these patterns may be helpful in FNAB diagnosis of rhabdomyosarcoma.

Two different forms of homozygous sickle cell disease occur in Saudi Arabia.

Haematological, clinical and some molecular genetic features of homozygous sickle cell (SS) disease in Saudi Arabia have been compared in 33 patients from the Eastern Province (Eastern) and 30 from the South Western Province (Western). Eastern patients all had the Asian beta globin haplotype whereas Western patients were more variable but predominantly of the Benin haplotype. Eastern patients had more deletional alpha thalassaemia, higher total haemoglobin and fetal haemoglobin levels, and lower HbA2, mean cell volume, reticulocytes, and platelet counts. Clinically, Eastern patients had a greater persistence of splenomegaly, a more normal body build and greater subscapular skin fold thickness, and Western patients had more dactylitis and acute chest syndrome. Painful crises and avascular necrosis of the femoral head were common and occurred equally in both groups. The disease in the Eastern province has many mild features consistent with the higher HbF levels and more frequent alpha thalassaemia but bone pathology (painful crises, avascular necrosis of the femoral head, osteomyelitis) remains common. The disease in the West is more severe consistent with the Benin haplotype suggesting an African origin.

Two different forms of homozygous sickle-cell disease - abstract

Haematological, clinical and some molecular genetic features have been compared in two groups of patients with homozygous sickle-cell (SS) disease in Saudi Arabia, 33 patients from the Eastern Province (eastern) and 30 from the South Western Province (Western). Eastern patients all had the Asian haplotype of DNA polymorphisms within the beta globin gene cluster whereas Western patients were more variable but predominantly of the Benin haplotype. Eastern patients had significantly more deletional alpha thalassaemia, higher levels of total haemoglobin and foetal haemoglobin, and lower of HBA, mean volume reticulocytes, and platelets. Clinically, Eastern patients had a greater persistence of splenomegaly, less dactylitis, less acute chest syndrome, a more normal body build and greater subscapular skin fold thickness. Painful crises occurred with equal frequency in both groups. Avascular necrosis of the femoral head was common in both groups. The disease in the Eastern province has many mild features consistent with the higher HbF levels and more frequent alpha thalassaemia but bone pathology (painful crises, avascular necrosis of the femoral head, osteomyelitis) remains common. The disease in the West is more severe, consistent with the Benin haplotype suggesting an African origin (AU)

Malignant rhabdoid tumor of the kidney presenting as intraocular metastasis.

A newborn infant presented with intraocular tumor that was clinically diagnosed as retinoblastoma and treated by exenteration of the globe. Within a few weeks however, a large abdominal mass was noted, which was found to involve the left kidney and right lobe of liver. Pathologic evaluation of the intraocular mass as well as fine-needle aspiration biopsy of the abdominal mass revealed features of malignant rhabdoid tumor. To our knowledge this is the first case of malignant rhabdoid tumor of the kidney with such an unusual clinical presentation.

Fine-needle aspiration biopsy diagnosis of malignant rhabdoid tumor of the kidney.

A series of six fine-needle aspiration biopsies from three patients with malignant rhabdoid tumor of the kidney is reviewed. The smears revealed round, polygonal, and irregularly shaped cells with large nuclei and prominent nucleoli. Some of the tumor cells contained light pink to purple cytoplasmic inclusions that correlated with the eosinophilic inclusions seen in histopathologic sections and filamentous cytoplasmic aggregates noted on ultrastructural examination. Diagnosis of malignant rhabdoid tumor of the kidney may be suggested from aspiration biopsy smears; however, further confirmation of the diagnosis by histologic or ultrastructural examination is desirable.

Radiosensitivity of fibroblasts obtained from a café-au-lait spot and normal-appearing skin of a patient with neurofibromatosis (NF-6).

Fibroblast cells derived from a café-au-lait spot and normal-appearing skin of a neurofibromatosis (NF-6) patient were studied for radiosensitivity in comparison with two normal cell lines used as "controls." No difference in radiosensitivity was observed between the patient's cell lines and the controls using acute gamma-irradiation. However, a markedly increased radiosensitivity of the fibroblasts obtained from the patient's skin of normal appearance was demonstrated after chronic gamma-irradiation. The cells from the café-au-lait spot showed intermediate sensitivity to chronic irradiation as compared with the control cell lines and the fibroblasts derived from the normal skin of the patient. These results showed the usefulness of chronic irradiation in detecting increased cellular radiosensitivity which may result from a unique DNA repair defect in an NF patient. We suggest that enhanced genetic changes in radiosensitive NF patients may lead to formation of café-au-lait lesions and certain tumors. Such a transformation may be associated with production of radiotolerant cells.

Fine-needle aspiration biopsy diagnosis of endodermal sinus tumor: histologic and ultrastructural correlations.

Fine-needle aspiration biopsies from five patients with endodermal sinus tumors (ESTs) were reviewed, and the findings were correlated with histologic and ultrastructural appearances. In the aspiration smears, two types of tumor cells were seen, forming clusters of variable sizes. Type A cells had distinct cell borders, and their cytoplasm contained only occasional vacuoles. Type B cells had ill-defined cell borders and formed syncytial clusters; their cytoplasm was characterized by large numbers of rounded vacuoles. The background contained patches of mucoid material and macrophages with foamy cytoplasm. Eosinophilic hyaline cytoplasmic bodies and irregular deposits of intercellular basement membrane-like material were recognized easily in aspiration smears. These features correlated well with histologic and ultrastructural appearances. The significance of these findings in the fine-needle aspiration biopsy diagnosis of EST and its distinction from other germ-cell and non-germ-cell tumors is discussed.

Endodermal sinus (yolk sac) tumor in infants and children. A clinical and pathologic study: an 11 year review.

We reviewed the clinical features, treatment, and results of children with gonadal and extragonadal yolk sac (endodermal sinus) tumors seen in the King Faisal Specialist Hospital and Research Centre between 1976 and 1987. There were nine children (seven girls and two boys) with ages ranging from 7 months to 12 years (median of 3.5 years). Sites of origin included the vagina (two cases), face (two cases), sacrum (two cases), mediastinum (one case), ovary (one case), and testicle (1 case). All children had elevated alpha-fetoprotein (AFP) at diagnosis. One girl had complete surgical excision of an ovarian tumor at the time of diagnosis, and one boy had surgical excision of the testis. In the remaining seven children, the tumor was unresectable. Surgery was limited to a biopsy in six children. All patients received different combinations of chemotherapy, including vincristine (VCR), actinomycin D (Act-D), cyclophosphamide (Cyclo), adriamycin (Adria), bleomycin (Bleo), cis-platinum (CDDP), vinblastine (VBL), and VP-16. Of the nine patients, one was lost to follow-up while in remission, five died, one was lost to follow-up, and three are alive and disease-free at 15, 55, and 67 months from diagnosis. This review demonstrates an unusual preponderance of the extragonadal form of endodermal sinus tumor among our patients.