Engraftment of human T-cell acute lymphoblastic leukemia in immunodeficient NOD/SCID mice which have been preconditioned by injection of human cord blood.

Childhood T-cell acute lymphoblastic leukemia (T-ALL) is one of the most common childhood cancers. Study of leukemia biology, as well as preclinical testing of potential therapeutic regimens directed at T-ALL, has been impeded by the lack of an efficient in vivo model of primary leukemia. We have reported elsewhere some observations that human cord blood conditioned medium enhances leukemia colony formation in vitro and preconditioning of sublethally irradiated nonobese diabetic/ severe combined immunodeficient (NOD/SCID) mice with cord blood mononuclear cells (MNCs) facilitates the subsequent engraftment of primary T-ALL cells in these mice. Here we characterize in greater detail this in vivo xenograft model of human leukemia in NOD/SCID mice. Consistent with the thesis that cord blood facilitates engraftment, the engraftment of human leukemia can be shown to increase with increasing number of cord blood MNCs injected. In addition, we documented the expression of chemokine receptor CXCR4 by primary T-ALL from patients and found that the presence of these receptors did not result in the transmigration of T-ALL cells induced by stromal cell-derived factor-1alpha. Finally, we show that in this xenograft system T-ALL cells recovered from engrafted bone marrow are characterized by upregulated expression of interleukin 2 receptor gamma chain, suggesting that cord blood preconditioning may function in part to increase T-ALL responsiveness to growth factor(s).

Cartilaginous choristoma of the nasopharynx.

A 21-year-old white male presented with persistent adenoiditis. A computed tomography (CT) scan with contrast was performed and was interpreted as normal. An adenoidectomy was performed, and histologic examination demonstrated the unexpected presence of a mature island of hyaline cartilage surrounded by lymphoid hyperplasia. The nature of this anomaly is considered in respect to the embryological development of the base of the skull and nasopharynx.

Giant juvenile xanthogranuloma of the tongue.

Juvenile xanthogranulomas (JXGs) are rare, benign, fibrohistiocytic lesions. They usually appear as one or more cutaneous papules on the head, neck, or trunk in infants. Twelve cases of oral JXGs have been reported, four of which involved the tongue. We present a 6-year-old girl with a large tongue mass diagnosed as JXG after an excisional biopsy. Histological and immunohistochemical staining results are presented. This is the first reported case of a giant oral JXG. A review of the literature on these unusual lesions is presented, along with discussion of their differential diagnosis and key aspects of the patient's evaluation, management, and pathological diagnosis.

Sudden death in Williams syndrome: report of ten cases.

Williams syndrome (WS) is a recognizable pattern of malformation with mental retardation, mild growth deficiency, characteristic facies and temperament, and cardiovascular disease. Sudden death is a recognized complication of WS; however, it is thought to be rare. The clinical features of 10 children with WS who died suddenly are reported here, doubling the number of unexpected deaths reported in the literature. We suggest that sudden death is a more common complication than has been assumed previously. Pathologic findings on the seven autopsy cases implicate two anatomic abnormalities that predispose individuals with WS to sudden death: coronary artery stenosis and severe biventricular outflow tract obstruction. The mechanisms for sudden death for both anatomic subgroups include myocardial ischemia, decreased cardiac output, and arrhythmia. We believe these observations warrant the development of strategies for monitoring patients with WS in an attempt to identify those at increased risk of sudden death.

Tetralogy of Fallot repair results in activation of the renin-angiotensin-aldosterone system.

Fluid retention is a common problem following transannular patch repair of tetralogy of Fallot. The present study was undertaken to evaluate whether humoral substances may contribute to this process. Patients undergoing tetralogy of Fallot repair using a transannular patch technique were compared to patients undergoing simple ventricular septal defect repair. Hormone levels were determined by radioimmunoassay. Fluid retention was defined as pleural effusions persisting beyond 5 days. The data demonstrate that patients undergoing tetralogy of Fallot repair had elevated levels of anti-diuretic hormone, renin, angiotensin II, and aldosterone as compared to a group with ventricular septal defect. The elevation in hormone levels in the tetralogy of Fallot group was principally accounted for by those who developed effusions postoperatively. These results suggest that activation of the renin angiotensin-aldosterone system may be one of the contributing factors to fluid retention following tetralogy of Fallot repair.

Fertility index analysis in cryptorchidism.

We report on 226 male patients with cryptorchidism 6 months to 16 years old who underwent open testis biopsy at orchiopexy or orchiectomy at Children's Hospital and Health Center from 1986 to 1990. A total of 355 specimens was obtained. Tissues were preserved in Bouin's solution and examined on light microscopy for fertility index measurements. Several biopsies prepared using Bouin's preserved paraffinized tissue and glutaraldehyde preserved semi-thin cut tissue were found to have comparable fertility index measurements. Of 184 patients with unilateral undescended testes 87 also underwent biopsy on the contralateral descended testis. A total of 42 patients had bilateral undescended testes. Age matched comparisons were made between fertility index measurements of the undescended testes and those previously reported of normal testes. Additional case matched comparisons of fertility indexes were made in those children who underwent biopsy of the undescended testis and its descended mate. Statistical analysis was performed using the independent Student t-test. When comparing undescended to descended testes, there was no significant difference in the fertility index of patients 1 year old or younger but fertility index differences were statistically significant in all of the other age groups. Fertility index measurements were significantly decreased from normal expected values in all age groups with unilateral cryptorchidism and in all but the 13 to 18-month-old group with bilateral cryptorchidism. The fertility index in the descended testis was similar to previously reported normal testis measurements in boys between 13 months and 6 years old. Our data suggest that potential fertility in the cryptorchid testis may be significantly impaired compared to normal testicular fertility regardless of patient age at the time of discovery of the undescended testis. The fertility index of the descended mates of unilateral undescended testes may also be somewhat impaired in certain age groups. Orchiopexy in the first year of life may be indicate to preserve available fertility potential.

Suppression of the pituitary thyroid axis after cardiopulmonary bypass in the neonate.

Thyroid hormone has numerous effects on cardiovascular function in the adult. The present study was undertaken to evaluate the effects of cardiopulmonary bypass and deep hypothermia on thyroid function in the neonate. Ten newborns were studied preoperatively and postoperatively. The total and free triiodothyronine, total and free thyroxine, thyroid-stimulating hormone, and thyroglobulin levels were measured by immunoassays. The data demonstrated a transient rise in the free thyroxine level associated with and followed by significant reductions in the free and total triiodothyronine, total thyroxine, thyroid-stimulating hormone, and thyroglobulin levels in the early postoperative period. By the fifth postoperative day, the free and total triiodothyronine and total thyroxine levels were returning toward the preoperative levels under the influence of an elevated thyroid-stimulating hormone level. These results suggest that the combination of cardiopulmonary bypass and deep hypothermia can result in a transient suppression of the pituitary-thyroid axis in the neonate.

Adenovirus myocarditis: retrospective diagnosis by gene amplification from formalin-fixed, paraffin-embedded tissues.

Understanding the pathogenesis of viral myocarditis is linked to the availability of sensitive assays to detect viruses in clinical material. Recent advances in molecular techniques permit direct detection of viral-specific nucleic acid in tissue samples. This report describes a protocol for DNA extraction and amplification of adenovirus genome from formalin-fixed, paraffin-embedded human tissues that detects as little as 10 copies of viral genome in a background of 0.5 micrograms of human DNA. This sensitive assay permitted the examination of archived tissues to establish a retrospective diagnosis of adenoviral myocarditis in two pediatric patients.

Pulmonary vasculitis with hemorrhage in anaphylactoid purpura.

We report a 14-year-old female with anaphylactoid purpura (AP) who developed pulmonary hemorrhage with acute vasculitis on lung biopsy. She improved with pulse methylprednisolone, daily prednisone and ventilatory assistance. Pulmonary vasculitis is a rare but serious manifestation of AP.

Comparison of the hormonal response after bidirectional Glenn and Fontan procedures.

Fluid retention is a frequent complication after the bidirectional Glenn and Fontan procedures. It was our hypothesis that this fluid retention may have a hormonal basis. To test this hypothesis, we made serial determinations of antidiuretic hormone, cortisol, aldosterone, angiotensin, and renin before and after operation in patients undergoing a bidirectional Glenn (n = 15) or Fontan (n = 18) procedure. Patients undergoing a bidirectional Glenn procedure had elevations in antidiuretic hormone, cortisol, and aldosterone immediately after operation. However, none of the hormonal elevations persisted by the fifth postoperative day. In contrast, patients undergoing a Fontan procedure had elevations in antidiuretic hormone, cortisol, aldosterone, renin, and angiotensin II in the immediate postoperative period. Five days postoperatively, the renin and angiotensin II levels remained elevated compared with the preoperative values. The data demonstrate that patients undergoing a bidirectional Glenn procedure and those undergoing a Fontan procedure have different patterns of hormonal response. These results suggest that hormonal factors may contribute to fluid retention after these operations.

Nasal hamartoma: case report and review of the literature.

Nasal masses in the pediatric population present with nasal obstruction, epistaxis and chronic rhinorrhea. We report on a 6-year-old boy with long-standing nasal obstruction. A large left nasal mass was evident on physical examination and CT scan. Techniques of functional endoscopic sinus surgery were used to resect the mass, which, on pathologic examination, proved to be a hamartoma. Hamartomas are non-neoplastic malformations, or inborn errors of tissue development. They are characterized by an abnormal mixture of tissues indigenous to that area of the body. Review of the literature revealed 5 previously reported cases of nasal hamartomas, only 2 of these in children. Our case is unique in that the hamartoma arose from the ethmoid and maxillary sinuses; previously reported cases arose from the septum and vestibule. This is the first reported case treated using a functional endoscopic sinus surgery approach.

Subcutaneous granuloma annulare: recognition and treatment.

Subcutaneous granuloma annulare (SGA) is a benign inflammatory disorder that occurs in children. The profiles of 12 children with SGA who were diagnosed and treated at our institution were reviewed. The patients presented with a rapidly growing, painless soft-tissue mass of the extremities or scalp. Parental concerns of malignancy and lack of recognition of this condition by the physician led to excessive diagnostic testing and, on occasion, inappropriate therapy. The mean age at presentation was 3.9 years, and the mean follow-up after biopsy study was 3.4 years. The lesions were most commonly located about the elbow, knee, and scalp. While complete blood count, erythrocyte sedimentation rate, and plain radiographs were helpful in ruling out other conditions, no ancillary test was specific for this disorder. In all cases, definitive diagnosis required a biopsy sample. Excisional biopsy was diagnostic but not therapeutic, because 75% of the children had one or more recurrences of this condition at either local or distant sites. Two of the subsequent lesions resolved spontaneously, and no child within the study group has progressed to any recognized systemic illness or connective-tissue disorder.

Ovarian germ cell tumor evolving to myelodysplasia.

We present the case of a 14-year-old girl in whom a myelodysplastic syndrome was diagnosed 9 months after surgical resection and chemotherapy for an ovarian germ cell tumor. Cells from her marrow were characterized by trisomy 8 and an isochromosome 12p, a marker that appears to be unique to germ cell tumors. The presence of the same two anomalies in her original tumor was demonstrated by fluorescence in situ hybridization study of interphase cells in paraffin-embedded tissues and thus provided strong evidence that the two neoplasms had a common clonal origin.

Mammalian epithelial cell line kit for detection of Clostridium difficile toxin.

The performance characteristics of a mammalian epithelial (MEP) cell line kit (Cytotoxi Test; Advanced Clinical Diagnostics, Toledo, Ohio) for the detection of Clostridium difficile toxin was compared with that of conventional tissue culture assays with human embryonic lung (HEL) cells in shell vials and human foreskin fibroblasts (HFFs) in test tubes. One hundred forty-nine stool samples were tested. The MEP cells were at least as sensitive as the HEL cells for use in C. difficile toxin detection. Results for the MEP cells were also obtained considerably more rapidly than those for HEL cells when the cells were examined at 4 and 24 h and then every 24 h for up to 5 days. Approximately one-third of all positive MEP cells were detected at 4 h and 95% were detected by 48 h. In comparison, in the HEL shell vial monolayers, only 6% of the positive cells were detectable at 4 h and 76% were detectable at 48 h. The times for C. difficile toxin-induced cytotoxicity in HFF cells were similar to those in HEL cells. Shell vials carrying HEL cell monolayers (ViroMed Laboratories Inc., Minnetonka, Minn.) are a sensitive and reliable commercial source for the detection of C. difficile toxin, although they cannot detect C. difficile as rapidly as the Cytotoxi test with the MEP cell monolayers.

The cryopreserved homograft valve in the pulmonary position: mid-term results and technical considerations.

Since September 1985, 60 cryopreserved homograft valves (12 aortic and 48 pulmonary) have been implanted in the pulmonary position in 56 patients. There were 34 primary operations and 26 reoperations. The ages ranged from 15 days to 22 years; the follow-up ranged from 1 month to 5 1/2 years. The operative mortality was 3.3% (2/56). There were two late deaths (not valve related). Five patients underwent replacement of the homograft; in one patient the homograft was replaced with a heterograft valve. Pathological analysis of the explanted homografts revealed calcification of the wall with satisfactory leaflet function. The leaflets were relatively acellular. No evidence of inflammation or rejection was detected. Four explants were performed for nonvalve-related indications. There are 51 long-term survivors with a homograft in place. Forty-eight are in excellent condition; three are mildly symptomatic (not valve related). Benign pulmonary insufficiency murmurs are present in 29 patients. The presence of trivial or mild insufficiency was independent of the technique of implantation. In general, cryopreserved homograft valves function well in the right ventricular outflow tract. Longer term follow-up is necessary to confirm the superiority of the cryopreserved homograft when compared to the porcine heterograft in the right ventricular outflow tract.

Actinomycosis in obstructive tonsillar hypertrophy and recurrent tonsillitis.

A quantitative analysis of adenoid and tonsillar specimens from 460 patients was performed. The patients underwent tonsillectomy or adenotonsillectomy for either recurrent tonsillitis or obstructive tonsillar hypertrophy. Histologic preparations revealed Actinomycetes as statistically more prevalent in the obstructive population. The presence of Actinomycetes in the adenotonsillar core of this diagnostic group may indicate an etiologic role for this organism in tonsillar and adenoidal hypertrophy.

Ischemic necrosis: a hypothesis to explain the pathogenesis of spontaneously ruptured enterocystoplasty.

Spontaneous enterocystoplasty rupture represents a devastating and potentially fatal late complication. Previously proposed mechanisms of rupture include catheter trauma, chronic infection, avulsion of adhesions between the bowel patch and peritoneum, and chronic overdistension with elevated intravesical pressures. We have witnessed this complication 4 times in 3 patients 5 weeks to 46 months postoperatively. Tissue specimens from 3 episodes in 2 patients with detubularized sigmoid enterocystoplasties were available for histological examination. All patients had a neurogenic bladder from myelomeningocele, all had an AMS800 artificial urinary sphincter and all had a documented history of chronic distension from inadequate emptying of the augmented bladder. At exploration, all of the ruptures were found within the bowel segment near the bladder apex in an area remote from the anastomotic line. In each case tissue specimens from the rupture site showed marked vascular congestion, intramural hemorrhage, abundant hemosiderin laden macrophages, myofiber atrophy and intravascular thrombi. These features are interpreted to reflect the sequelae of vascular compromise and ischemia. We propose that enterocystoplasty rupture results from ischemia, possibly due to chronic overdistension and subsequent vascular compromise. This mechanism may account for many of the previously reported cases of enterocystoplasty rupture.

Germ cell neoplasms of head and neck soft tissues: a pathologic spectrum of teratomatous and endodermal sinus tumors.

Germ-cell neoplasms, in particular teratomas with immature and mature somatic type tissues, are some of the most commonly found tumors in children. Approximately 5% of these neoplasms appear in one of several extracranial sites in the head and neck region. This study reports the clinical, pathologic and immunohistochemical findings in six germ-cell neoplasms occurring in the neck and facial areas. A mass was recognized at birth in five children, and the sixth patient was 2 1/2 years old at diagnosis. Four of the six neoplasms contained one or another element of endodermal sinus tumor; two of these had a mixed pattern of endodermal sinus tumor and teratoma. The other two cases were purely teratomas. The serum alpha-fetoprotein was known to be elevated in three children whose tumors had endodermal sinus elements; it returned to normal level in two of the children, but remained high in the one fatal case. Placental alkaline phosphatase and alpha-fetoprotein were demonstrated immunohistochemically in two of the three cases, with available tissue containing endodermal sinus tumor. Teratomatous metastases in ipsilateral cervical lymph nodes were found in one patient with a pure teratoma; that patient is disease-free one year after surgery. Only nine previous examples of endodermal sinus tumor have been reported in the head and neck region, exclusive of the central nervous system. There is one other case in the literature of a congenital cervicothyroidal teratoma with metastatic disease. These six neoplasms illustrate the clinical and pathologic spectrum in this nosologically homogeneous, but morphologically diverse, category of tumors.