Case 1

BETTE K. KLEINSCHMIDT-DeMASTERS
University of Colorado School of Medicine
Denver, CO

Clinical Summary:

The patient is a 23-year-old right handed female who first experienced difficulties in 05/2001 when she stopped taking her birth control pills and noted the onset of headaches. Over the next several months the headaches became progressively worse and were particularly painful around the time of her menstrual periods. She subsequently was started back on her birth control pills in 11/2002 and her headache improved, but because she wanted to try to become pregnant she once again ceased taking her birth control pills in 05/2002. Her headaches returned. After she stopped taking her birth control pills in 05/2002 she developed amenorrhea, but no galactorrhea. Her gynecologist saw her in 02/2003 and a prolactin level was found to be moderately elevated at 103 ng/ml. MRI scan demonstrated a 1.9 X 2.3 X 1.5 cm. sellar and suprasellar mass abutting the optic chiasm, with displacement of the normal gland superiorly and to the right. The patient was referred to an endocrinologist. More extensive workup verified the elevated prolactin level but showed normal levels of TSH, free T4, LH, and FSH. IGF-1 level was 426 (normal 182-780) and beta HCG was not detectible. The clinical impression was that the tumor was unlikely to be a prolactin-secreting adenoma due to its size and only modest elevation in prolactin; stalk effect was suspected.

On 05/19/2003, she underwent transsphenoidal resection of her pituitary adenoma without complications. Postoperatively she did well except for persistent left-sided headaches that she described as sharp and virtually daily in occurrence, albeit of less severity than those she experienced preoperatively. Menstruation returned but again the headaches were worse during this time period.

Postoperative neuroimaging revealed good reduction in overall tumor mass, but persistent residual enhancing tissue in the left cavernous sinus. This was not felt to be resectable and was thought to be the likely source of the patient's continuing headaches.

On follow up examination in 09/2003 she complained of a low energy level, with persistent fatigue. One observer thought there was "a vague suggestion of acromegaly" due to her somewhat coarse facial features. Repeat laboratory studies showed normal FSH, LH, IGF-1, T-4, TSH, cortisol, and prolactin. On 10/16/2003, the patient was treated with stereotactic radiosurgery, with 15 gray delivered to the left cavernous sinus lesion; she tolerated the procedure well.

Case 1 - Figure 1 - Pituitary adenoma component of the mixed pituitary adenoma-gangliocytoma shows a patternless sheet of monomorphic cells and demonstrates features indistinguishable from a pure pituitary adenoma.

Case 1 - Figure 2 - Prolactin immunostaining reveals an irregular distribution of staining throughout the tumor, with up to 50% of the adenoma population immunoreactive for this hormone in some areas.

Case 1 - Figure 3 - Growth hormone immunostaining was also irregularly distributed but clearly was present in a much smaller percentage of the adenoma population.

Case 1 - Figure 4 - A sharp junction was apparent between the pituitary adenoma component and the ganglion cell portions of this tumor. Note the very large numbers of ganglion cells near this junction.

Case 1 - Figure 5 - Ganglion cells, some of which are binucleate, are embedded in neuropil-like, finely fibrillar matrix.

Case 1 - Figure 6 - Prolactin immunostaining was identifiable in some of the binucleate cells within the gangliocytoma areas.

Case 2

RICHARD A. PRAYSON
Cleveland Clinic Foundation
Cleveland, OH

Clinical Summary:

A 45-year-old woman presented with a 6 day history of ascending sensory loss and weakness of the left leg progressing to complete sensory loss, dense paraparesis of both legs and bladder/bowel incontinence. Other than Graves' disease, which was recently treated with iodine131 followed by thyroxine replacement, the patient's medical history was unremarkable. T2-weighted magnetic resonance imaging (MRI) showed a non-enhancing fusiform area of increased signal at at the thoracic (T2-3) level of the spinal cord and a single area of increased signal in the deep cerebral white matter. The patient was treated with an 8 day course of i.v. ACTH followed by a tapering oral prednisone regimen.

One month later the patient presented with no significant improvement in symptoms. Neurological examination at this time found minimal hip flexor anti-gravity strength and no ankle dorsi-flexor anti-gravity strength of the lower extremities bilaterally with grade 1 spasticity. Vibration and joint position sense were absent to the level of the knee and hip joint, respectively. Reflexes in the lower extremities were pathologically brisk with positive Babinski's signs. Examination of the cranial nerves and upper extremities revealed no deficit. Relevant laboratory tests included the following (normal range in paretheses): hemoglobin, 159 g/l (120-160); leukocyte count, 5.24x109/1 (4.0-11.0) with neutrophils 82.6%, lymphocytes 11.1%; platelets, 145 K/ul (150-400); erythrocyte sedimentation rare, 1.0 mm/h (0.0-20.0); serum albumin, 3140 mg/dl (3276-4819); serum IgG, 582 mg/dl (747-1470); CSF protein, 45 mG/dl (15-45); CSF red cell count, 1 (0-1/ul); CSF white cell count, 1 (0-3/ul); CSF IgG, 4.0 mg/dl (0.6-4.4); CSF albumin 29.2 m/dl (9.3-31.3); CNS IgG synthesis, 1.6 mg/dl (0.0-30.0); IgG/albumin ratio, 0.14 (0.06-0.17); IgG index, 0.50 (0.00-0.61); lactate dehydrogenase (LDH), 1776 U/l (100-220): Oligoclonal bands, antinuclear antibodies (ANA), rheumatoid factor, syphilis serology (RPR, HA-TP) and SF cultures for bacteria, herpes virus and fungi were negative. Cytological examination of the CSF, bone marrow and peripheral blood did not demonstrate neoplastic cells. A repeat MRI scan of the spinal cord and brain showed numerous hyperintense lesions in the right periventricular white matter and thoracic spine (T2-3), interpreted as being consistent with demyelinating disease. Steroid therapy was commenced.

Despite steroid therapy, the patient was readmitted on several occasions for worsening paraplegia, sensory deficits, hearing loss and cognitive impairment. Further MRI studies of the brain showed no new interval changes.

Ten months after initial presentation, a sigmoid colostomy was performed for bowel atony and severe obstipation. Two weeks later, the patient was admitted for recurrent seizures, multiple electrolyte abnormalities, acute hepatic and renal failure and infected decubitus ulcers. Neurological examination demonstrated a right facial paresis, dysarthria, no anti-gravity strength in the lower extremities and positive Babinski's signs bilaterally. A sensory level at T8 was demonstrated and joint position/vibration was absent in both lower extremities. The patient continued to decline with worsening renal function, severe metabolic acidosis and multiple tonic/clonic seizures prior to death.

Case 2 - Figure 1 - Low magnification view of the cortex showing involvement of vessels in the leptomeninges as well as cortical parenchyma by the lymphomatous process (hematoxylin and eosin, original magnification 100x).

Case 2 - Figure 2 - High magnification appearance of lymphomatous cells within vascular lumina. Cells are marked by irregular nuclear contours and high nuclear to cytoplasmic ratio. Extension of lymphomatous cells beyond vascular walls was not observed (hematoxylin and eosin, original magnification 400x).

Case 2 - Figure 3 - The intervascular tumor cells stain positively with antibody to CD20 indicating a B-cell immunophenotype (CD20 immunostain, original magnification 400x).

Case 2 - Figure 4 - CD3 immunostain shows rare positive staining benign T lymphocyte cells within and around vessels in the leptomeninges. The tumor cells themselves do not stain with CD3 (CD3 immunostain, original magnification 250x).

Case 3

ROGER E. McLENDON
Duke University Medical Center
Durham, NC

Clinical Summary:

The patient was a 3-year-old white male diagnosed with a posterior fossa brain tumor after presenting with wide based gait, nausea, vomiting, headache and "the room being upside down." A head CT revealed a 4 cm mass in the left lateral cerebellum displacing the 4th ventricle and both the 3rd and lateral ventricles were enlarged. He underwent near total resection on 1/29/93 and pathology revealed the present tumor without invasion of the brain stem.

He has subsequently been followed by his local medical doctor.

Case 3 - Figure 1 - The tumor is diagnosed by its unique secondary structures, the ribbons and papillae that form an abortive neurotubular epithelium. These structures exhibit a stratified or pseudostratified lining of elongated cells that superficially form a linear, epithelioid arrangement and centrally abut a vascular structure. Cytologically, the tumor cells are devoid of cilia thereby distinguishing them from tumors of ependymal or choroid plexus cells.

Case 3 - Figure 2 - The tumor is diagnosed by its unique secondary structures, the ribbons and papillae that form an abortive neurotubular epithelium. These structures exhibit a stratified or pseudostratified lining of elongated cells that superficially form a linear, epithelioid arrangement and centrally abut a vascular structure. Cytologically, the tumor cells are devoid of cilia thereby distinguishing them from tumors of ependymal or choroid plexus cells.

Case 4

DANIEL J. BRAT
Emory University Hospital
Atlanta, GA

Clinical Summary:

A 32-year-old female developed headaches and blurred vision over the course of three months. Magnetic resonance imaging (MRI) revealed a large, contrast-enhancing suprasellar mass with multiple cystic components. The tumor impinged on the optic chiasm superiorly and extended posteriorly and inferiorly into the posterior fossa, where it compressed the right side of the pons. The neoplasm was surgically resected. Follow-up MRI after 12 months showed no residual tumor.

Three years after the operation, the patient developed progressively worsening back and leg pain, lower extremity weakness, as well as bowel and bladder dysfunction. She required a wheelchair and could not walk without assistance. MRI of the spinal cord showed a contrast-enhancing intradural mass that filled and expanded the thecal sac, extending from the T12 to the S1 level. At surgery, the tumor was found to entrap spinal cord and spinal roots. It also eroded through the dura in multiple locations. The tumor was resected piece by piece from the surrounding normal structures. The specimen from the spinal resection was sent for pathological examination.

Case 4 - Figure 1 - Pre- and post-contrast sagittal MR images of the spine showing an intradural mass extending from the T12 to the S1 level. The tumor distends the thecal sac and obliterates the view of the spinal cord.

Case 4 - Figure 2 - Pre- and post-contrast axial MR images of the spine demonstrating a solid, homogeneous mass greatly expanding the thecal sac within the vertebral canal and extending into soft tissues posteriorly.

Case 4 - Figure 3 - Low magnification H&E-stained section of clear cell meningioma showing a homogeneous tumor of moderate cellularity with a clear cell population and abundant intracellular hyaline stroma.

Case 4 - Figure 4 - High magnification H&E-stained section of clear cell meningioma showing tumor cells with clear, glycogen-rich cytoplasm and round, bland nuclei. Intracellular hyaline stroma is deposited in spherical configurations and shows multifocal, punctate crystalline deposits.

Case 4 - Figure 5 - H&E-stained cytologic smear preparation of clear cell meningioma demonstrating classic meningothelial cytologic features including whorls, delicate nuclear chromatin, and wispy cytoplasm.

Case 5

GREGORY N. FULLER
MD Anderson Cancer Center
Houston, TX

Clinical Summary:

A 49-year-old woman presented with a solitary, contrast-enhancing mass of the left frontal lobe measuring approximately 3cm in greatest diameter as assessed by MR imaging. An open biopsy was performed.

Case 5 - Figure 1 - Epithelioid Glioblastoma. This variant of glioblastoma exhibits a prominent epithelioid morphology that can closely mimic metastatic melanoma and other epithelioid neoplasms (H&E, X400).

Case 5 - Figure 2 - Epithelioid Glioblastoma. Confirmation of the diagnosis is provided by demonstrating immunopositivity for glial fibrillary acidic protein (GFAP). Epithelioid glioblastomas do not show reactivity for melanoma markers (GFAP; X400).