Gleb N. Budzilovich

Treatment and Survival of Low-Grade Astrocytoma in Adults--1977–1988

A retrospective review of the records of the Division of Neuropathology at the New York University Medical Center between 1977 and 1988 revealed 53 cases of adult supratentorial astrocytomas. Fifty were fibrillary, and three were gemistocytic. Two additional patients had pilocytic tumors and were not included in the study. The majority of patients had either a subtotal (64%) or gross total resection (19%). Biopsy (17%) was performed for deep-seated lesions and for those lesions confined to eloquent cortex. Forty-eight patients (91%) received postoperative radiation therapy. The median survival was 7 1/4 years with a 5-year survival of 64%. Multivariate regression analysis demonstrated that the most important prognosticators for improved survival were young age, absence of contrast enhancement of the original tumor on computed tomography (CT) and the performance status of the patient. Patients with hemispheric tumors died from dedifferentiation into an anaplastic astrocytoma or a glioblastoma multiforme, with a median time to recurrence of 4.5 years from the original surgery. Survival from the time of recurrence was 12 months. Subsequent operations confirmed progression towards malignancy in six of seven (86%) recurrent tumors. CT contrast enhancement of the original tumor was associated with a 6.8-fold increase in risk for later recurrence. Patients with thalamic tumors (six patients) had a poor prognosis with a median survival of less than 2 years. A review of their CT scans suggest that four died of progressive low-grade disease; however, confirmatory autopsy data were available for only one patient. This study supports others that have shown improved survival for adult patients with astrocytomas treated in the CT era.

Improved long term survival after intracavitary interleukin‐2 and lymphokine‐activated killer cells for adults with recurrent malignant glioma

Background. The median survival for adults with glioblastoma multiforme (GBM) is 12 months, despite surgery, radiation, and chemotherapy. Regimens using interleukin‐2(IL‐2) plus lymphokine‐activated killer (LAK) cells have been beneficial against systemic cancers, albeit with significant toxicity.

Demyelinating disease versus tumor in surgical neuropathology. Clues to a correct pathological diagnosis.

Clinical presentations as well as radiological and histopathological findings in biopsies from patients with multiple sclerosis (MS) or other demyelinating disorders of the central nervous system are sometimes misleading, resulting in an erroneous diagnosis of brain or spinal cord tumor. We report 17 patients who presented with symptoms mimicking those of brain (14 cases) or spinal cord (three cases) tumors. Computerized tomography or magnetic resonance imaging studies or both were interpreted as consistent with a tumor in each case. All patients underwent surgery, and all 17 pathological specimens were eventually diagnosed as showing demyelinating disease, usually consistent with MS. In each case we examined a variety of histological features and immunohistochemical studies and addressed their relative importance in considering the diagnosis of MS. All cases showed perivascular lymphocytic inflammation with variable amounts of macrophage infiltration, necrosis, and edema. The hypercellularity of the lesions and the presence of atypical reactive astrocytes with mitotic figures were the disturbing features that might have led to the erroneous diagnosis of an astrocytic neoplasm. Immunohistochemistry for astrocytic (glial fibrillary acidic protein) and macrophage (HAM-56) markers are helpful in evaluating biopsies. Our results emphasize the need to perform special stains (i.e., for myelin and axons) that demonstrate myelin loss and relative preservation of axons and allow a correct diagnosis.

Synaptophysin: A sensitive and specific marker for ganglion cells in central nervous system neoplasms

Synaptophysin, a 38-kilodalton glycoprotein found in synaptic vesicle membranes, has been shown to be a sensitive marker of neuroendocrine differentiation in non-central nervous system (CNS) tumors. We analyzed the patterns of synaptophysin immunoreactivity in CNS neoplasms in comparison with various normal CNS sites in biopsies. Normal gray matter structures all showed a diffuse punctate granular pattern of neuropil staining without staining of neuronal cell bodies. In contrast, neoplastic ganglion cells in 18 of 18 gangliogliomas/gangliocytomas showed intense immunoreactivity outlinging the borders of the cell bodies. Focal staining was also seen in five of 16 primitive neuroectodermal tumors and in one of three central neurocytomas, but these tumors had a finely granular neuropil pattern of immunoreactivity more like that of normal gray matter than like that of the gangliogliomas. All 35 examples of pure gliomas of various types showed no immunoreactivity. Our data highlight synaptophysin as a sensitive and specific marker of both neuronal lineage and neoplastic character in gangliogliomas.

A study of rod-like structures (Hirano bodies) in 240 normal and pathological brains

SummaryA study of rod-like structures (RLS) was made in 173 pathological and in 67 normal brains. The pathological brains included cases with varied neuropathological conditions: vascular, metabolic, degenerative, infectious, traumatic, neoplastic, etc. The ages of the patients ranged from newborn to 97 years. RLS were found in 152 pathological brains (89%) and in 50 normal brains (75%). RLS were localized in all but one case, in Ammons horn, specifically in Sommers sector and in the stratum lacunosum beneath Sommers sector. There was no correlation between any group of diseases studied and appearance or number of RLS. The number of RLS in Sommers sector increased with advancing age. In the middle age, ihowever, the stratum lacunosum showed a higher number of RLS. The results of this study idicate that there is no significant relationship between RLS and any pathological condition and therefore that they represent non-specific changes, although a correlation with advancing age is probable. Although RLS appeared to be intracellular, their exact localization was not established.

Prognostic relevance of epidermal growth factor receptor (EGF-R) and c-neu/erbB2 expression in glioblastomas (GBMs)

SummarySeventeen untreated primary adult glioblastomas were analyzed using immunocytochemistry for the expression of EGF-R, c-neu/erbB2, TGF-α, and phosphotyrosine. Patients were divided by median survival into long-term or short-term survivors (LTS, N=10, median > 4 years; versus STS, N=7, median 61 weeks). There were no significant differences between the two groups in terms of age, extent of resection, post-operative Karnofsky status, or treatment. Diagnostic sections from each tumor were stained with antibodies to EGF-R, c-neu/erbB2, TGF-α and phosphotyrosine. Double-labelling for TGF-α and EGF-R was also performed. All 10/10 LTS were considered to be EGF-R negative/scant, while 4/7 STS were EGF-R positive. EGF-R negativity significantly correlated with long-term survival. The differences in c-neu/erbB2 expression did not reach significance. However, 4/7 STS were positive for both proteins and 76% of the 17 cases were either double negative or positive for EGF-R and c-neu/erbB2. TGF-α and phosphotyrosine were frequently expressed, but neither were prognostic. Recurrent tumors were studied in 7 STS. EGF-R expression was increased in 4/7 of these cases and c-neu/erbB2 was increased in all 7 cases, compared to the pretreatment baselines. Increased expression of these proteins in glioblastomas may be associated with aggressive clinical behavior and treatment resistance.

Brain and spinal cord hemorrhage in long‐term survivors of malignant pediatric brain tumors: A possible late effect of therapy

Three children with malignant primary CNS tumors treated with craniospinal radiotherapy developed intraparenchymal hemorrhages a median of 5 years following therapy in sites distant from the primary tumor. Radical surgical procedures disclosed fresh and old hematoma, gliosis, and necrosis in all 3 patients and an aggregation of abnormal microscopic blood vessels in two. No tumor was found. All 3 patients remain in long-term (>10 years) continuous remission.

Brain abscess due to Actinobacillus actinomycetemcomitans.

INFECTION IN MAN by actinobacillosis has recently been described.l.2 This is the first report of a cerebral abscess caused by actinobacillus and affords opportunity for pathological study of this infection involving brain. The causative organism, Actinobacillus actinomycetemcomitans, is an obscure, gram-negative aerobic bacillus which was first found in 1912 together with Actinomyces israelii in human actinomycosis.l Classified under Brucellaceae, a family which also includes Pasteurella, Haemophilus, and Brucella, the genus Actinobacillus is formed around the type species Actinobacillus lignieresii, an organism originally cultured from bovine actinomycosis in 1902.3 Distinction between A. actinomycetemcomitans and A. lignieresii cannot be made from the original descriptions, since only crude characteristics were specified, and the precise status of earlier reports is unknown.

Sensory, motor, and autonomic dysfunction: The nervous system in familial dysautonomia

FAMILIAL DYSAUTONOMIA is a complex and poorly understood disease which was first described in 1949 under the title, “Central autonomic dysfunction with defective‘ lacrimation.”l Since that time, additional clinical observations have led to the establishment of criteiia for diagnosk24 These criteria include autosomal recessive inheritance with Jewish parentage, defective lacrimation, vasomotor instabilities, poor temperature control, and episodic hyperhidrosis. In addition to abnormalities attributable to the field of action of the autonomic nervous system, there are sensory disturbances which include corneal anesthesia, indifference to pain, and impaired taste sensation. Indicators of neuromuscular dysfunction are poor coordination and absent or hypoactive deep tendon reflexes. Body growth is often retarded and mental development is slow. Pharmacologic and physiologic studies have amplified the clinical data and to some extent aided in understanding the disease.5-14 Reports of anatomic pathologic defects in dysautonomia have been very varied and, as in the case of pharmacologic and physiologic studies, have not permitted the development of a single unifying concept of this still perplexing disea~e.1,15-~0 Our studies of a 1-year-old child with familial dysautonomia have revealed findings, some of which have not been previously reported, which may help to clarify this disease and may aid in distinguishing it from other ill-understood clinical syndromes with certain similarities.21-23

The lipid-rich epithelioid glioblastoma.

The authors add to the literature an account of four aggressive glial neoplasms characterized by diffuse cytoplasmic lipidization and a cohesive architectural disposition in epithelioid nests and sheets. These neoplasms arose in the cerebral hemispheres of adults and tended to a circumscribed neuroradiologic presentation that in two instances prompted an unrewarding preoperative search for an extracranial primary. One represented recurrent disease in a patient being followed for a biopsy-proven low-grade astrocytoma: Three cases were collected by way of consultation from pathologists uncertain as to their primary versus metastatic derivation. The apparent expression of cytokeratins and epithelial membrane antigen further conspired to obscure the glial lineage of these peculiar neoplasms, which are best regarded as tumors of the astrocytic series.