Faculty Bibliography

The rapid diagnostic techniques of smears and frozen sections are fundamental to the strategy of the neuropathologist in evaluating tissue received at the time of operating room consultation with the neurosurgeon. This strategy begins with the exclusion of nonneoplastic lesions and proceeds to determination of the neoplastic cell type, or, in the case of reoperation of a treated tumor, the distinction of viable from necrotic tumor. In the interest of conserving unfrozen tissue for permanent sections, a smear may be made and examined initially, with a frozen section prepared only if the smear is equivocal or technically inadequate. This approach has been shown to result in a degree of diagnostic accuracy comparable to that described in general surgical material subject to frozen section analysis.

Oligodendrogliomas are indolent brain tumors with mean postoperative survival of about 5 years. However, the range of postoperative survivals is wide, suggesting that these tumors are heterogeneous in their biologic behavior. Using restriction fragment length polymorphism (RFLP) analysis, we studied a case of an oligodendroglioma with loss of chromosome 10 sequences, a finding that has only been reported in glioblastoma multiforme and anaplastic astrocytomas. Four and a half months after the initial surgery the patient returned with a recurrent tumor having classic radiologic and pathologic features of glioblastoma multiforme. Loss of chromosome 10 alleles in oligodendroglioma may be predictive of aggressive biologic behavior, even in the absence of recognized histopathologic characteristics of anaplasia, and may enable us to select more appropriate treatments for this group of patients.

Congenital sensory neuropathies associated with arthrogryposis multiplex congenita (AMC) are rare. We report a unique case of a nine-week-old, full-term infant with AMC, congenital sensory neuropathy, and posterior column degeneration. The family history was negative for neuromuscular disease. At birth, the infant was small for gestational age, indicative of intrauterine growth retardation. He was hypotonic and hyporeflexic, and failed to sustain respiration. He remained ventilator-dependent throughout his life. Electrodiagnostic studies indicated widespread peripheral neuropathy. At two weeks of age, biopsied sural nerve was almost completely devoid of myelinated axons; quadriceps skeletal muscle contained only mild and nonspecific abnormalities. Autopsy showed pulmonary hypoplasia. The major nervous system findings were severe, bilateral posterior column degeneration, mild posterior horn gliosis, atrophy of posterior roots, and axonal degeneration of the peripheral nerves. Sensory and autonomic (vagal) nerves were preferentially involved, with relative sparing of motor nerves. This case suggests that interruption of kinesthetic pathways early in gestation may result in fixed joints.

A cavernous angioma of the posterior fossa dura was discovered incidentally on neuroimaging studies. The clinical and pathologic features of this lesion are described. Although it has been reported to arise in the posterior fossa and the tentorium cerebelli, we present the first case of such a malformation arising from the dura of the posterior fossa.

A 56-year-old woman with ovarian papillary cystadenocarcinoma that metastasized to the pituitary gland sought treatment with a 7-day history of total loss of vision in one eye. Ten days after transsphenoidal tumor resection, the patient's vision suddenly returned to baseline. This unusual case indicates that surgical decompression of the optic nerve and chiasm can completely salvage vision, even after prolonged total visual loss.

Conventional imaging techniques are often unreliable in distinguishing between radiation necrosis and recurrent glioma in patients who are symptomatic after high-dose radiotherapy. We performed dual-isotope single-photon emission computed tomography (SPECT) with the use of thallium-201 (201TI) and the perfusion agent 99mTc-hexamethyl-propyleneamine oxime (HMPAO) to aid in this differentiation in 15 patients with glioma prior to biopsy. We found that dual-isotope SPECT scanning correlated with the pathologic findings in 14 of the 15 cases. All patients with high 201TI uptake in their treated tumor beds had local tumor recurrence, and all patients with low 201TI uptake showed only radiation changes without evidence of solid tumor. In patients with an intermediate level of 201TI concentration in their tumor bed, 99mTc-HMPAO uptake differentiated those patients with active tumor from those without; three of four patients with preserved or increased perfusion had pathologic evidence of solid tumor, whereas none of the four patients with decreased perfusion to the tumor bed had evidence of local recurrence. We believe that dual-isotope SPECT with 201TI and 99mTc-HMPAO may be useful in differentiating sites of likely tumor growth from nonspecific radiation changes in patients treated for malignant glioma.

The recent recognition of the eosinophilia-myalgia syndrome (EMS) associated with the ingestion of L-tryptophan prompted an analysis of the peripheral blood eosinophil phenotypes and of the serum eosinophil hematopoietins in this disorder. Five patients with an illness characterized by the abrupt onset of aching skeletal muscles, edema, thickening and induration of the skin, and marked blood eosinophilia associated with L-tryptophan ingestion provided eosinophils, serum, or both, for evaluation. Gradient sedimentation density analysis of the peripheral blood eosinophils from four of these patients revealed that 43 +/- 13% (mean +/- SEM) of the cells had converted to the abnormal (hypodense) sedimenting phenotype. When normodense eosinophils from the reference donors were cultured for 3 days in medium supplemented with increasing concentrations of serum from the patients with EMS, their viability increased in a dose-dependent manner to 45%, which was significantly augmented over the effect of normal serum. This eosinophil viability-sustaining activity was inhibited by 76 +/- 7% (mean +/- SEM; n = 3) by the addition of anti-interleukin 5 (IL-5) but not by neutralizing antibodies monospecific for either granulocyte/macrophage colony-stimulating factor (GM-CSF) or IL-3. IL-5, an eosinophilopoietic factor, converts normodense peripheral blood eosinophils in vitro to a hypodense sedimenting form with extended viability and augmented biologic responses to activating stimuli. Thus, the presence of IL-5 in the sera of patients with EMS may contribute to the development and maintenance of the eosinophilia and may regulate the conversion of the peripheral blood eosinophils to the hypodense phenotype with augmented pathobiologic potential.

In the oral cavity, differentiation between reactive and neoplastic lymphoproliferative lesions can, at times, be very difficult. We report an unusual case in which immunohistochemical findings were necessary to determine that the lesion was reactive despite the original interpretation of malignant lymphoma. The relationship of this lesion to atypical histiocytic granuloma, angiolymphoid hyperplasia with eosinophilia, and traumatic ulcerative granuloma with stromal eosinophilia is discussed and possible pathogenetic mechanisms are proposed. The value of immunohistochemistry in the diagnosis of extranodal lymphoproliferative lesions is emphasized.