Annette D. Segura

Inflammatory myofibrohistiocytic proliferation simulating sarcoma in children

The term “inflammatory myofibrohistiocytic proliferation” (IMP) has been proposed to replace the conventional designations of plasma cell granuloma and inflammatory pseudotumor. Three cases of extrapulmonary IMP in children are reported, including an intracerebral lesion which has been formerly undescribed. In children, IMP may be associated with microcytic hypochromic anemia, hypergammaglobulinemia, and high erythrocyte sedimentation rate. In this clinical setting, differentiation of a rapidly growing but benign IMP from a bona fide sarcoma is of paramount importance.

Neonatal hypotonia and cardiomyopathy secondary to type IV glycogenosis

A neonate with deficiency of branching enzyme (glycogenosis type IV) presented symptoms of severe hypotonia pre- and postnatally, and dilated cardiomyopathy in early infancy. The classical clinical manifestation of liver cirrhosis was not present, although amylopectin-like inclusions were found in the hepatocytes. In contrast to a previous report, the neurons in the brain stem and spinal anterior horns contained PAS-positive, diastase-resistant deposits. The combined involvement of the muscles and motor neurones could account for the severity of hypotonia. The muscle biopsy, electromyogram and biochemical and enzyme assays were helpful in establishing the diagnosis.

Dermatomal lichenoid chronic graft-vs-host disease following varicella-zoster infection despite absence of viral genome

Localized cutaneous graft‐versus‐host disease (GVHD) following a dermatomal distribution or in a pattern of Blaschkos lines. Some authors have postulated that dermatomal GVHD is triggered by a varicella‐zoster virus infection, although in reported cases, there was no history of a preceding herpes zoster. We describe a case of GVHD localized to the exact dermatome of a culture‐proven varicella‐zoster virus infection. PCR analysis failed to detect persistence of viral genome in the affected skin.

Congenital Volkmann ischaemic contracture: a case report and review.

Congenital Volkmann ischaemic contracture or neonatal compartment syndrome has rarely been discussed in the literature of dermatology. The condition often involves the upper extremity with cutaneous lesions, contractures and neuropathy. Because the lesions can be mistaken for other entities including necrotizing fasciitis, neonatal gangrene, congenital varicella, aplasia cutis congenita, amniotic band syndrome, subcutaneous fat necrosis and epidermolysis bullosa, dermatologists play a significant role in the diagnosis and, consequently, the treatment of the patient. We describe a premature newborn who had a unilateral, well‐demarcated necrotic plaque with a central pallor at birth. The plaque extended circumferentially over the left forearm from the wrist to the elbow. Left wrist oedema, bullae over the fingers and flaccid paralysis at the wrist were also noted.

Spontaneous, persistent infection of a B-cell lymphoma with adenovirus

An adenovirus culture‐positive lymphoblastoid cell line was derived from a bone marrow transplant recipient with fatal B‐cell lymphoproliferative disease and adenovirus pneumonia. At autopsy, focal areas of the lymphoma infiltrating the patients lung were positive for adenovirus proteins by immunohistochemical staining. The Epstein‐Barr virus‐transformed B‐cell line Mk, established from pleural fluid cells, contained adenovirus virions in both the nucleus and the cytoplasm by electron microscopy. The majority of Mk cells expressed adenovirus proteins and produced a high level of infectious adenovirus by plaque assay analysis. However, in contrast to the rapid cell death induced by adenovirus in other permissive cell lines, Mk was maintained stably in tissue culture for 6 months. These data indicate that adenoviral replication is not sufficient for cell lysis and confirm that adenovirus can cause persistent infection in human lymphoid cells in vivo.

Infiltrating T cells during liver graft-versus-host disease show a restricted T-cell repertoire

Data from animal models have shown that hepatic graft-versus-host disease (GVHD) may be mediated by donor T cells interacting with liver adhesion molecules, other minor histocompatibility antigens, or both. We hypothesized that T-cell infiltrates within a liver biopsy during clinical GVHD would show a restricted T-cell response because the T cells would be responding to a limited number of antigens. We studied the peripheral T-cell repertoire and the liver-infiltrating T-cell repertoire of a patient who developed skin GVHD and subsequent liver GVHD after a matched sibling bone marrow transplantation for acute myeloid leukemia. Spectratype analysis of peripheral blood at the time of liver GVHD revealed that the patient had reconstituted a complex peripheral T-cell repertoire as evidenced by the presence of complementarity-determining region 3 (CDR3) length heterogeneity in most of the T-cell families. The repertoire complexity was skewed in variable gene beta (VB) 5.3, VB4, VB7, VB8, and VB15. Spectratype analysis on the liver biopsy sample revealed a limited infiltrate with an oligoclonal expansion in VBs 4, 7, and 8. We evaluated the T-cell infiltrate in more detail by sequencing the relevant expansions noted by spectratype and developing probes for the predominant CDR3 sequences. These clonotype probes were hybridized to peripheral blood and liver samples from the patient, a T-cell line developed from the patients peripheral blood at the time of the initial skin GVHD, the donors blood and marrow, and control samples. The results showed that the T-cell infiltrate during liver GVHD is mediated by a limited number of T cells, and that those cells are mostly different from the ones expanded from the peripheral blood during an acute skin GVHD reaction. These data support the concept that liver GVHD is a response to tissue-specific minor histocompatibility antigens.

Osteoblastoma response to chemotherapy

An 8‐year‐old boy had an osteoblastoma of the body of C2. After attempted excision, the tumor recurred rapidly and massively. The tumor shrank progressively after treatment with high‐dose methotrexate, doxorubicin, and cisplatin. The patient has stopped treatment and been stable for 33 months. Surgical excision remains the treatment of choice for osteoblastoma. Chemotherapy may be useful in selected patients with a recurrent, aggressive tumor or in patients with surgically inaccessible disease.

Selective incorporation of111In-labeled PHOTOFRIN™ by glioma tissuein vivo

The use of PHOTOFRIN™ for photodynamic therapy of human gliomas has been studied by i.v. administration and laser photosensitization. Defining the uptake of PHOTOFRIN™ in the patients tumor in comparison with the surrounding normal brain tissue is highly desirable for patient selection and study ofin vivo kinetics. We utilized a non-invasive approach to the detection of PHOTOFRIN™ uptake in brain tumors with111In-oxine radiolabeled PHOTOFRIN™ and external imaging and quantitation using a gamma camera. Biodistribution of111In-labeled PHOTOFRIN™ in 13 organs was determined in four dogs and 15 mice with gliomas.99mTc-DTPA was used as a control for nonspecific uptake. The greatest concentration of111In-PHOTOFRIN™ in the brain tumor occurred at 24 hours post i.v. administration. The brain tumor PHOTOFRIN™ uptake was seven times greater than that of normal brain. The decreased blood background at 72 hours made this the optimum time for imaging. Specific tumor tissue uptake of111In-PHOTOFRIN™ occurred, well beyond that resulting from blood-brain-barrier (BBB) breakdown.

Anesthesia-induced rhabdomyolysis in infants with unsuspected Duchenne dystrophy

Anesthesia‐induced rhabdomyolysis in infancy may represent an unsuspected Duchenne dystrophy. In order to establish the diagnosis of this genetic disease more definitively, a dystrophin test is a requisite following the conventional creatine kinase test and light and electron microscopies of the muscle biopsy.

Prevention of gallium toxicity by hyperhydration in treatment of medulloblastoma

In vitro and in vivo studies have established gallium nitrate as an effective chemotherapeutic agent against human medulloblastoma. In vitro, gallium nitrate reduced cell proliferation and DNA synthesis of medulloblastoma Daoy. Gallium inhibits the availability of 59Fe to ribonucleotide reductase and has a direct effect on the enzyme itself. In vivo, gallium demonstrated similar effects on the medulloblastoma Daoy cell line in nude mice. Tumor growth rate and actual size were decreased; however, severe nephrotoxicity and mortality were observed. In our study, intradermal injections of medulloblastoma Daoy cells were given to nude mice and then tumors were allowed to grow. Tumor-bearing mice received a 15-day gallium (50 mg/kg/day) regimen, 20-day rest, 7-day gallium (66.5 mg/kg/day) dose escalation regimen beginning when tumor size exceeded 8-10 mm in diameter. All treated and control mice received saline hyperhydration during both treatment sessions. Our study resulted in the prevention of severe toxicity and an inhibition of tumor growth. No toxicity occurred with gallium nitrate at 50 mg/kg/day. Severe morbidity and mortality were observed at the higher gallium dose level (66.5 mg/kg/day), suggesting that the 50 mg/kg/day dose is the appropriate level when investigating gallium nitrate as a chemotherapy agent in nude mice.