Association between mediastinal germ cell tumors and hematologic malignancies. Report of two cases and review of the literature.

A hematologic malignancy occurred simultaneously with a malignant mediastinal germ cell tumor in two men. In one instance the blood disorder was acute nonlymphocytic leukemia, and in the other, malignant histiocytosis. We subsequently identified nine additional patients, all male (age range 12-48 years), with a mediastinal germ cell tumor and either acute nonlymphocytic leukemia or malignant histiocytosis. Six of the 11 patients had not received either radiation or chemotherapy before development of the hematologic malignancy. One patient developed malignant histiocytosis and was found to have a malignant mediastinal germ cell tumor after having received steroid therapy for a renal allograft. The four remaining patients developed acute nonlymphocytic leukemia 5-32 months after initiation of irradiation or chemotherapy for a mediastinal germ cell tumor. In four patients with acute leukemia, karyotypic analysis established the clonal nature of the leukemic process. Although the leukemia may be therapy-related in four or possibly five patients, this explanation cannot be applied to the remaining six patients. These six patients, coupled with studies of in vitro growth characteristics of teratocarcinoma cells described previously, suggest that a previously unrecognized association between malignant mediastinal germ cell tumors and hematologic malignancies may exist in humans.

Primary lymphomas of the liver. Report of six cases and review of the literature.

Six cases of diffuse large cell lymphoma (DLCL) of the liver were studied with immunohistochemistry for common leukocyte antigen (CLA), lysozyme, alpha-1-antitrypsin (AAT), and kappa and lambda light chains on paraffin-embedded tissues. All six cases were positive for CLA. Four of the six cases showed staining for lysozyme and AAT (three focal and one diffuse staining). In three cases, frozen tissue for monoclonal antibodies and glutaraldehyde-fixed tissue for electron microscopic examination were available. Two of these showed B-cell phenotypes with monoclonal antibody studies. Electron microscopic examination on these two B-cell lymphomas showed scant cytoplasm and a paucity of cytoplasmic organelles. The third case did not show definite B- or T-cell surface markers but did show strong Leu-M1 and OKM1 staining. Electron microscopic examination of the tumor cells showed a prominent Golgi apparatus, abundant cytoplasm with numerous cytoplasmic organelles and phagolysosomes. However, DNA hybridization studies on this tumor showed immunoglobulin heavy and kappa light chain gene rearrangements typical of a B-cell lymphoma. All six lymphomas were solitary liver masses without evidence of disease elsewhere. The mean age for the six patients was 56.2 years (four males, two females).

Malignant epithelioid peripheral nerve sheath tumor arising in a benign schwannoma.

The case of a patient with malignant degeneration of a solitary abdominal schwannoma and endobronchial metastasis is presented. The patient presented clinically with dyspnea referable to her lung mass, anorexia, and night sweats. The lung mass, initially diagnosed as a large-cell undifferentiated carcinoma, was later found to be histologically identical to the malignant portion of the abdominal tumor. The light microscopic, electron microscopic, and immunoperoxidase staining characteristics of the tumor are reported, and previous reports in the literature are reviewed.

Diagnosis of central nervous system Toxoplasma gondii from the cerebrospinal fluid in a patient with acquired immunodeficiency syndrome.

The cytologic diagnosis of central nervous system (CNS) Toxoplasma gondii was established from the cerebrospinal fluid (CSF) in a patient with acquired immunodeficiency syndrome (AIDS) who presented with obstructive hydrocephalus and progressive obtundation. Free extracellular tachyzoites, phagocytized tachyzoites, and cyst forms were identified with Wright staining of cytocentrifuge preparations. Diagnosis was confirmed with indirect immunofluorescent antibody studies. Initial CSF examination was remarkable for low cellularity (24 wbc/mm3) with 42% neutrophils and 58% mononuclear cells on differential examination. Subsequent differential counts of CSF showed persistence of a mixed inflammatory pattern until day 10 at which time a mononuclear pleocytosis was observed. Cerebrospinal chemistries were notable for a low glucose (20 mg/dl), which persisted for 10 days. The cytocentrifuge Wright stain preparation was found to be superior to routine millipore filter Papanicolaou stain preparation for the identification of free tachyzoites and is recommended in the setting of immunodeficient patients with suspected CNS toxoplasmosis.

Lead exposure in an "urban" peregrine falcon and its avian prey.

Necropsy of a 7-yr-resident peregrine falcon (Falco peregrinis) from Baltimore showed a Pseudomonas infection involving the pharynx as the immediate cause of death. Concentrations of lead in liver and kidney measured 0.74 and 1.40 ppm, respectively. A survey of lead exposure was performed on 40 urban rock doves (Columbia livia). Thirteen additional rock doves were collected from sites removed from lead contamination and served as controls. The mean concentration of lead in the blood of the urban rock doves was 0.96 ppm (range 0.29-17.0 ppm) compared to 0.05 ppm (0.01-0.07 ppm) for control birds. Ninety-eight percent (39/40) of the urban rock doves had elevated concentrations of lead in their blood, while 27% (11/40) had sublethal concentrations. None of the control birds had increased concentrations of lead in their blood. Concentrations of lead in liver and kidney of 13 urban rock doves were 3.48 ppm and 9.53 ppm, respectively, compared to concentrations of 0.43 ppm and 0.50 ppm for four control rock doves. From these data a mean total concentration of lead per rock dove was calculated at 4.60 ppm for urban birds and 0.33 ppm for control birds.

Toxic lead exposure in the urban rock dove.

Thirteen adult urban rock doves (Columba livia), 12 captured alive and one found dead, were studied from the Baltimore zoo. The mean concentration of lead in the blood for the 12 live birds was 184.5 +/- 531.2 (range 10.5-1,870 micrograms/dl). Three of the 13 birds with high measured blood and tissue lead concentrations were found at necropsy with lead shot pellets in their gizzards. Correlations were not found between concentrations of lead in the blood and body weight or hematocrit. Conversely, high correlations were noted between concentrations of lead in the blood and measured liver and kidney concentrations (r = 0.946, P less than 0.01; r = 0.993, P less than 0.01, respectively). Numbers of intranuclear acid-fast inclusions per 10 consecutive fields (100x oil immersion lens) correlated well with measured kidney lead concentrations (r = 0.990, P less than 0.001).

Common leukocyte antigen staining of a primitive sarcoma.

A 4-year-old boy presented with symptoms of tracheal obstruction and was found to have a polypoid tracheal mass, which was studied by biopsy. Light microscopy showed a tumor composed of small cells with round to oval dark nuclei, clumped chromatin, one to two nucleoli, and small, variable amounts of indistinct pink cytoplasm. In other areas the tumor had a loose, spindle appearance, with some cells showing more elongated nuclei, and fibrillar pink cytoplasm consistent with strap cells. Cross striations were not found. Electron microscopy showed desmosomes and 7 to 10 nm cytoplasmic filaments forming dense bodies. The findings are most consistent with a primitive sarcoma, probably rhabdomyosarcoma. Immunoperoxidase with three monoclonal antibodies for common leukocyte antigen showed diffuse membraneous staining with fresh-frozen tissue. All other lymphocyte and monocyte marker studies were negative. We believe that this case of anticommon leukocyte antigen staining, a rhabdomyosarcoma, represents the first report of a false positive reaction with monoclonal antibody to common leukocyte antigen.

Interactions of vitamin E and penicillamine in the treatment of hereditary avian muscular dystrophy.

Our prior work demonstrated that penicillamine treatment of dystrophic chickens delayed the onset of symptoms, partially alleviated contractures, improved muscle function, and lowered serum creatine kinase. Penicillamine, a sulfhydryl compound with reducing properties, also prevented inactivation of glycolytic enzymes by protecting thiol groups. The present study shows that vitamin E enhances the therapeutic effects of penicillamine. Interaction of these two reductants is dose related. With vitamin E as adjunct therapy, the dosage level of penicillamine could be lowered by 50%, thereby minimizing side effects. The therapeutic rationale for two antioxidants is that penicillamine may act primarily in the cytoplasm to prevent oxidative damage, whereas the more hydrophobic vitamin E may protect membrane bilayers. Additionally, penicillamine may prevent collagen cross-linking and, deposition of insoluble collagen in muscle and thus decrease contracture formation. General applications of combined penicillamine and vitamin E therapy are discussed regarding prevention of free radical and oxidative damage in Duchenne dystrophy and a wide range of human diseases.

Peripartum myocarditis and cardiomyopathy.

The clinical and pathologic features of 18 consecutive patients with peripartum cardiomyopathy at The Johns Hopkins Hospital were examined in an attempt to define the incidence of myocarditis and to determine its response to immunosuppressive agents. In addition to routine studies, patients were evaluated with echocardiography, nuclear ventriculography, right heart catheterization, and myocardial biopsy. Fourteen of the 18 patients (78%) showed evidence of myocarditis. Of these, 10 were treated with immunosuppressive therapy. Nine of the 10 treated patients with myocarditis had subjective and objective improvement. Follow-up endomyocardial biopsies in these patients showed resolution or substantial improvement in myocarditis. Four patients with myocarditis not treated with immunosuppressives also improved. All patients improving spontaneously presented with congestive heart failure within 1 month of delivery and improved dramatically within days of presentation. Four of the 18 patients showed no evidence of myocarditis. Of these, two improved, and two deteriorated (both requiring cardiac transplantation). None of these four patients were treated with immunosuppressive therapy. We conclude that in patients with peripartum cardiomyopathy, 1) the etiology remains unclear although myocarditis was present in 78% of those with this condition, 2) resolution of myocarditis is associated with significant improvement in left ventricular function, 3) myocarditis may resolve spontaneously without detectable loss of cardiac function, and 4) immunosuppressive therapy in patients with myocarditis and persistent left ventricular dysfunction may improve left ventricular function and prognosis.