Faculty Bibliography

Congenital cystic adenomatoid malformation (CCAM) encompasses a spectrum of variably cystic developmental anomalies of the lung histologically characterized by immature lung tissue. The pathogenesis is uncertain, but many investigators favor a maturation arrest in bronchopulmonary development. To investigate this hypothesis, the vascular development and proliferation capacity of lung tissue with CCAM type I from nine infants ranging in age from 20 weeks gestation to 42 days old were studied immunohistochemically utilizing CD34 for the former and MIB-1 for the latter. Both markers were quantitated on an image analysis system. CCAM was hypovascular with a mean vascular index of 20.05% +/- 6.58 compared to 40.06% +/- 4.19 for the age-matched controls (P < 0.000001). The proliferation index of both epithelial and mesenchymal components was higher in CCAM (10.46 +/- 3.48) than in control tissue (7.14 +/- 1.88; P < 0.012). In contrast to the control lung tissue which showed a remarkable synchrony between the vascular development and proliferation throughout the parenchyma, focal asynchrony between the proliferation of the epithelial and stromal components was noted in CCAM. The vascularity in CCAM corresponds to that seen in early gestation. The cellular proliferation in CCAM is higher than in full-term infants and corresponds to late second trimester or early third trimester fetuses. These findings support the proposed pathogenesis of a maturation defect in lung embryogenesis

We investigated the expression and distribution of the extracellular matrix protein tenascin (TN) in 59 astrocytomas and 11 samples of normal brain by Western blot analysis and immunohistochemistry using antibodies against human TN. The tumors included 14 juvenile pilocytic astrocytomas (grade 1), 13 low grade fibrillary astrocytomas (grade II), 8 anaplastic astrocytomas (grade III), and 24 glioblastomas multiforme (grade IV). Proliferation indices were calculated by computer-based image analysis after immunostaining with the MIB-1 antibody against the Ki-67 proliferation-associated antigen. Western blot analysis for TN on fresh frozen tumor tissue from 23 of the 59 astrocytomas indicated up to 4-fold higher TN expression in glioblastomas multiforme than in nontumorous control tissues. Enhanced intercellular expression of TN was observed by immunohistochemistry in glioblastomas multiforme. More-over, TN immunostaining was consistently greater within and around the walls of hyperplastic blood vessels than nonhyperplastic vessels of both high grade tumors and juvenile pilocytic astrocytomas. Juvenile pilocytic astrocytomas with increased TN expression by Western blot analysis had vascular hyperplasia by light microscopy. Proliferation indices moderately correlated with tumor grade. Enhanced immunohistochemical expression of TN was associated with higher tumor grade with higher proliferation indices. The strong association of TN and vascular hyperplasia, regardless of tumor grade, suggests that TN may play a crucial role in angiogenesis

Proliferative breast disease (PBD) is a well-recognized histologic entity that has received increasing attention in the cytologic literature. We have attempted to prospectively identify and subclassify PBD by fine needle aspiration biopsy since 1987 using criteria we developed through our experience. Over 2800 breast FNABs were performed on breast lesions from 1987 to mid-1992; 257 were cytologically diagnosed as PBD with or without atypia. Eighty-four were significantly worrisome clinically to warrant surgical excision. Forty of these were designated PBD without atypia by cytology; 23 (58%) were in agreement with histology; three (8%) were PBD with atypia by histology; five (13%) were cancers; and nine (22%) were nonproliferative. Forty-four cases were designated PBD with atypia; 24 (55%) were in agreement with the histologic diagnosis; 12 (27%) proved to be PBD without atypia; six (13%) were carcinoma; and two (5%) were nonproliferative. After 1991 we employed stricter criteria for PBD, improving on the results from 1991-1992. During this period, there were 53 diagnoses of PBD with or without atypia and 34 were excised. Nine of the 10 (90%) aspirates designated as PBD without atypia were in agreement with histologic findings. The other case was nonproliferative. Fifteen of the 24 cases diagnosed as PBD with atypia were in concordance with histologic findings (63%), one was nonproliferative, seven were PBD without atypia (29%), and one (4%) proved to be carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatoblastoma, although rare, is the most common primary malignant neoplasm of the liver in children. In this paper we describe a case of hepatoblastoma with unusual cytologic features and present the histologic, immunocytochemical and ultrastructural features of this neoplasm. A 7-month-old girl presented with a large hepatic mass and metastatic nodules in both lungs. Intraoperative biopsy revealed a hepatoblastoma. Aspiration biopsy yielded a highly cellular aspirate with cords of pleomorphic cells embedded in a mucoid matrix. Histologic sections showed a diffusely infiltrative neoplasm composed of sheets and cords of highly pleomorphic cells. The neoplastic cells stained strongly positive for cytokeratin CAM 5.2 and AE1 and focally positive for alpha-fetoprotein, ferritin, carcinoembryonic antigen and vimentin. Ultrastructurally, the neoplastic cells had abundant intercellular junctions and intracytoplasmic aggregates of intermediate filaments. A mucoid matrix, to our knowledge, has not been reported as a finding on aspiration biopsy. This patient presented with pulmonary metastases, and thus we think the mucoid matrix may be a marker of a more aggressive variant of hepatoblastoma. This case illustrates additional cytologic features of hepatoblastoma and the usefulness of aspiration biopsy in the rapid diagnosis of this rare tumor.

We have discussed the causes of lymphocytopenia and attempted to categorize them according to pathogenesis. This effort may be tenuous at best, because so much is still unknown about lymphocyte function and kinetics. In describing pathogenesis we have reported what has been published and not speculated on mechanisms when they were not stated. Many of these reports were decades apart, and the technical resources available to the investigators were varied. We suspect, for example, that many of the lymphocyte changes secondary to inflammation and infection will have a common pathogenesis (for example, cytokines and endotoxins). Undoubtedly, the picture will become much clearer in the years ahead.

Mucosal neuromas (MN), a component of multiple endocrine neoplasia (MEN) type IIb, may be confused histologically with plexiform neurofibromas (PN), a component of neurofibromatosis. The ability to distinguish between these two markers for different genetic diseases is crucial, as the risk of development of medullary thyroid carcinoma and pheochromocytoma in affected patients with MEN IIb is great. We studied two cases each of MN and PN by immunocytochemistry (IC). Epithelial membrane antigen (EMA) proved to be the most useful marker. MN consisted of bundles of disorganized and tortuous nerve fibers surrounded by a thickened perineurium that expressed the cellular phenotype EMA(+), S-100(-). PN consisted of enlarged nerve fascicles with a loose myxoid stroma and was EMA negative. Thus, IC highlighted the differing pattern of growth and histogenesis of the proliferating cells in the two lesions and is likely to be especially useful in those lesions with atypical histology

A 13-year-old boy with Down syndrome (DS) had a brainstem glioma confirmed at autopsy, 10 years after receiving prophylactic cranial irradiation for acute myeloblastic leukemia. There is no clear association of brain tumors with DS; despite a reported link between leukemia and glioma, a causal association with radiation therapy is more likely

A 13-month-old immunocompetent girl had fever, rash, and multisystem disease, and she eventually died of cardiac failure. Autopsy revealed intracellular viral inclusions of the herpesvirus group, with results of in situ hybridization positive for human herpesvirus-6. This is apparently the first case of fatal disseminated herpesvirus-6 infection