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Protocol for the Examination of Specimens From Patients With Tumors of the Brain/Spinal Cord.

A Basis for Checklists

This protocol is intended to assist pathologists in providing clinically useful and relevant information as a result of the examination of surgical specimens. Use of this protocol is intended to be entirely voluntary. If equally valid protocols or similar documents are applicable, the pathologist is, of course, free to follow those authorities. Indeed, the ultimate judgment regarding the propriety of any specific procedure must be made by the physician in light of the individual circumstances presented by a specific patient or specimen.

It should be understood that adherence to this protocol will not guarantee a successful result. Nevertheless, pathologists are urged to familiarize themselves with the document. Should a physician choose to deviate from the protocol based on the circumstances of a particular patient or specimen, the physician is advised to make a contemporaneous written notation of the reason for the procedure followed.

The College recognizes that this document may be used by hospitals, attorneys, managed care organizations, insurance carriers, and other payers. However, the document was developed solely as a tool to assist pathologists in the diagnostic process by providing information that reflects the state of relevant medical knowledge at the time the protocol was first published. It was not developed for credentialing, litigation, or reimbursement purposes. The College cautions that any uses of the protocol for these purposes involve considerations that are beyond the scope of this document.

PROTOCOL FOR THE EXAMINATION OF SPECIMENS FROM PATIENTS WITH TUMORS OF THE BRAIN/ SPINAL CORD
 I. Cytologic Material
 A. Clinical information
 1. Patient identification
 a. Name
 b. Identification number
 c. Age (birth date)
 d. Gender
 2. Responsible physician(s)
 3. Date of procedure
 4. Other clinical information
 a. Relevant history (note A)
 b. Relevant findings (note B)
 c. Clinical/imaging differential diagnosis
 d. Procedure (eg, percutaneous fine-needle
 aspiration)
 e. Anatomic site of specimen (note C)
 B. Macroscopic examination
 1. Specimen
 a. Unfixed/fixed (specify fixative) (note D)
 b. Number of slides received, if appropriate
 c. Cytologic preparation of tissue specimen
 (touch or squash preparation)
 2. Material submitted for microscopic evaluation
 (eg, smear of fluid, cell block) (note E)
 3. Special studies (eg, cytochemistry, immunocytochemistry,
 microbiology, flow cytometry)
 (note F)
 C. Microscopic evaluation
 1. Adequacy of specimen for diagnostic evaluation
 (if unsatisfactory or limited, specify reason)
 2. Tumor
 a. Histologic type, if possible (note G)
 3. Other pathologic findings
 4. Results/status of special studies (specify)
 5. Comments
 a. Correlation with intraoperative consultation
 b. Correlation with other specimens
 c. Correlation with clinical information
 (note H)
 II. Biopsy
 A. Clinical information
 1. Patient identification
 a. Name
 b. Identification number
 c. Age (birth date)
 d. Gender
 2. Responsible physician(s)
 3. Date of procedure
 4. Other clinical information
 a. Relevant history (note A)
 b. Relevant findings (note B)
 c. Clinical/imaging differential diagnosis
 d. Procedure (eg, stereotactic needle core biopsy,
 open biopsy)
 e. Anatomic site of specimen (note C)
 B. Macroscopic examination
 1. Specimen
 a. Unfixed/fixed (specify fixative) (note D)
 b. Size (number of cores or size of biopsy in
 dimensions or approximate volume)
 c. Descriptive features (grossly obvious meninges,
 gray matter or white matter, color,
 texture, cut surface, mucinous, fibrous,
 bloody, necrotic, gritty)
 d. Recognition of gross and microscopic correlates
 is helpful in correct interpretation of
 microscopic findings and is also helpful in
 selecting cores for frozen section analysis
 2. Special studies (note F)
 a. Frozen sections, if requested
 b. Squash, touch, or scrape preparations
 c. Histochemistry
 d. Immunohistochemistry
 e. Electron microscopy
 f. Other (microbiology, flow cytometry, cytogenetics,
 molecular diagnostics)
 g. Was a portion of tissue frozen for later potential
 studies?
 3. Tissue submitted for microscopic evaluation:
 The specimen is usually totally submitted after
 removing tissue for frozen sections, electron
 microscopy, or other special studies as
 indicated in note F. Try to orient at right angles
 to surface.
 C. Microscopic evaluation
 1. Tumor
 a. Histologic type (note I)
 b. Histologic grade (note J)
 c. Additional features, if present
 (1) Hemosiderin deposition
 (2) Calcification
 (3) Microcyst formation
 (4) Mitotic activity
 (5) Pleomorphism
 (6) Presence of gemistocytes
 (7) Vascular proliferation
 (8) Necrosis
 d. Findings in squash, touch, or scrape preparations
 (note K)
 2. Status/results of special studies (specify)
 3. Comments
 a. Correlation with intraoperative consultation
 b. Correlation with previous specimens
 c. Correlation with clinical information
 (note H)
III. Resection
 A. Clinical information
 1. Patient identification
 a. Name
 b. Identification number
 c. Age (birth date)
 d. Gender
 2. Responsible physician(s)
 3. Date of procedure
 4. Other clinical information
 a. Relevant history (note A)
 b. Relevant findings (note B)
 c. Clinical/imaging differential diagnosis
 d. Procedure (total, subtotal, or partial resection)
 e. Operative findings
 f. Anatomic site of specimen (note C)
 B. Macroscopic examination
 1. Specimen
 a. Unfixed/fixed (specify fixative) (note D)
 b. Number of pieces with combined aggregate
 dimensions (the extent of resection
 can have prognostic significance) (note A)
 c. Descriptive features (grossly obvious meninges,
 gray matter or white matter, color,
 texture, cut surface, mucinous, fibrous,
 bloody, necrotic, gritty)
 d. Recognition of gross and microscopic correlates
 is helpful in correct interpretation of
 microscopic findings and is also helpful in
 selecting cores for frozen section analysis
 e. Margins, as appropriate. For the majority
 of central nervous system neoplasms, margins
 are not evaluated because specimens
 are fragmented. Exceptions would be some
 meningeal or metastatic tumors.
 f. Results of intraoperative consultation
 2. Tissue submitted for microscopic evaluation.
 The specimen is usually totally submitted after
 removing tissue for frozen sections, electron
 microscopy, or special studies, as suggested
 in note F.
 3. Special studies (note F)
 a. Frozen sections, if requested
 b. Squash, touch, or scrape preparations
 c. Histochemistry
 d. Immunohistochemistry
 e. Electron microscopy
 f. Receptor analysis
 g. Other (microbiology, flow cytometry, cytogenetics,
 molecular diagnostics)
 h. Was a portion of tissue frozen for later potential
 studies?
 C. Microscopic evaluation
 1. Tumor
 a. Histologic type (note I)
 b. Histologic grade (note J)
 c. Local extension (eg, bony or soft tissue invasion,
 subarachnoid spread; note K)
 d. Additional features, if present
 (1) Hemosiderin deposition
 (2) Calcification
 (3) Microcyst formation
 (4) Mitotic activity
 (5) Pleomorphism
 (6) Presence of gemistocytes
 (7) Vascular proliferation
 (8) Necrosis
 e. Findings in squash, touch, or scrape preparations
 (note K)
 2. Status/results of special studies (specify)
 3. Comments
 a. Correlation with intraoperative consultation
 b. Correlation with previous specimens
 c. Correlation with clinical information
 (note H)


EXPLANATORY NOTES

A: Relevant History.--Patient Age.--Most central nervous system (CNS) tumors show an age predilection, and patient age has been shown to predict survival in many malignant CNS neoplasms. With diffusely infiltrating astrocytic tumors, age followed by histologic grade represent the 2 strongest prognostic indicators for patient outcome, with patient age older than 50 years and high-grade tumors serving as negative indicators.[1-4]

Duration of Symptoms (Acute or Chronic).--A long clinical history of CNS symptoms or seizures prior to the diagnosis of a CNS tumor favors a slowly growing neoplasm that is more likely to be benign. A rapidly progressive neurological deficit of sudden onset is more consistent with, but not always indicative of, a high-grade malignant tumor.[5]

Extent of Resection.--For most CNS tumors, the amount of tumor removed (total, subtotal, or partial resection) is an important predictor of patient outcome.[3,4,6]

The extent of resection can be estimated by recording the gross dimensions of the aggregate pieces. In most operating rooms, a suction device is frequently used in conjunction with gross debulking to remove tumors. We recommend that the surgical team be encouraged to submit the suction specimen to surgical pathology. This will serve to better estimate the extent of resection, and the tissue present in the suction specimen might be critical in making the correct diagnosis.

Tumor Location and Size.--The extent of surgical resection possible is determined by tumor location and size.

Previous Diagnoses.--Knowledge of the presence or absence of extracranial disease, that is, a history of immunosuppression or a history of a primary malignant neoplasm outside the CNS, can be critical in the correct interpretation of biopsy material.[5] If a metastatic tumor is included in the differential diagnosis, it is helpful to have slides of the primary tumor available.

Previous CNS Biopsies.--History of radiation or radiosurgery.--Knowledge of prior radiation therapy or radiosurgery can help in interpreting specimens in which there are large areas of radiation change (eg, coagulative necrosis, gliosis, vascular hyalinization).[7(pp125,126)] Central nervous system tumors noted to arise in a field of prior irradiation include meningiomas, meningeal sarcomas, astrocytomas, primitive neuroectodermal tumors, and gliosarcomas.[7(pp586-587)] Radiation therapy of diffusely infiltrating astrocytomas has been shown to increase survival.[3,8]

Family History of Cancer or Primary CNS Tumors.

B: Relevant Findings.--Imaging Features (density; enhancement pattern; well-circumscribed or infiltrative borders; cyst formation; calcification; location [intraventricular]; white matter, gray matter, or both).--Recognition of characteristic imaging patterns and locations of CNS tumors is important in correct interpretation of biopsy specimens, for example, low-grade infiltrating astrocytomas usually do not enhance, whereas high-grade ones do.[5] Tumor enhancement and peritumoral edema in infiltrating astrocytomas are associated with a worse prognosis, and diffuse tumors have been shown to have a poorer prognosis than focal ones.[9,10]

C: Anatomic Site of Specimen.
Cytologic Material

Cerebrospinal fluid (ventricular, lumbar, cisternal)
Cyst fluid
Fine-needle aspiration
Percutaneous (specify site)
Stereotactic computed tomography-guided
Other

Biopsy or Resection

Dura (convexity, falx, tentorium, sphenoid wing, skull base)
Leptomeninges
Cerebrum (specify lobe: frontal parietal temporal, occipital)
Basal ganglia
Thalamus
Hypothalamus
Pituitary
Suprasellar area
Pineal
Cerebellum (specify lobe: right or left hemisphere, midline
 or lateral)
Cerebellopontine angle
Ventricle (third, lateral, fourth)
Brain stem (midbrain, pons, or medulla)
Spine (extradural, intradural/extramedullary, intradural/
 intramedullary, conus medullaris, filum terminale)
Nerve root(s)/canal (extradural, intradural, anterior root
 or posterior root)


D: Specimen Unfixed/Fixed.--Cytologic Material.--Cytologic preservation in cerebrospinal fluid depends on the time interval before processing, especially for hematopoietic and some neuroepithelial cells. Refrigerate if delayed more than 30 to 45 minutes. Record the time interval to aid in interpretation.

Biopsy or Resection.--Cellular detail is very important for interpreting CNS neoplasms, and previously frozen tissue is suboptimal, especially for grading and subclassifying gliomas. Recommendations for optimally freezing and cutting frozen sections from tissue from the brain and spinal cord have been made in a previously published article.[5] Make every attempt to retain tissue that has not been previously frozen for permanent sections. Avoid using sponges in cassettes because they produce angular defects, which resemble vascular/luminal spaces in the final sections. Wrapping small biopsies in lens paper prior to placing them in cassettes is recommended.[5]

E: Cytologic Material Submitted for Microscopic Evaluation.--Cytospin slides or liquid-based monolayer cytology, both air-dried Romanowsky-stained and fixed Papanicolaou-stained slides, as well as unstained slides, should be prepared from fluid specimens, especially cerebrospinal fluid, meningeal fluid, and tumoral cyst fluid.

F: Special Studies.--It may be necessary to divide biopsy/resection tissue into portions for the following procedures:

1. Squash, touch, or scrape preparations

2. Unfrozen permanent paraffin sections

3. Frozen sections, if requested

4. Electron microscopy (retain a small portion in 3% glutaraldehyde or "embed and hold" for electron microscopy if necessary)

5. Other (microbiology, flow cytometry, cytogenetics, molecular diagnostics)

6. Frozen tissue, if requested (freeze fresh tissue as soon as possible and store at -70 [degrees] C), especially for possible future molecular diagnostic studies

When the tissue is a biopsy and the tissue sample is small the order of priority for processing tissue for the procedures outlined above is as listed. Recommendations for optimally freezing and cutting frozen sections from tissue from the brain and spinal cord have been made in a previously published article.[5] If biopsy frozen and permanent sections are nondiagnostic, tissue that was retained in 3% glutaraldehyde could be submitted for electron microscopy or for additional paraffin sections, depending on the amount of tissue available, with the hope of making a diagnosis. Some pathologists may choose to examine semithin or 1-[micro]m-thick stained sections with toluidine blue instead.

Squash preparations are prepared by placing a tiny (1-2mm) fragment of tissue onto a glass slide, placing another glass slide over it, pressing the slides together, squashing the tissue between them, then sliding the 2 slides past each other, dragging squashed tissue across each slide. Slides are then rapidly placed into fixative in the same rack used for frozen sections and stained as for frozen sections.[5]

Squash preparations are recommended for most CNS lesions. Touch preparations are recommended for pituitary adenomas, oligodendrogliomas, and lymphomas. Scrape preparations, in which tissue is scraped with a scalpel blade and scrapings are applied to glass slides and stained similar to squash and touch preparations, are recommended for desmoplastic tumors, such as dural metastases that cannot be squashed or do not shed well on touch preparations.

If infectious etiologies are suspected, a portion of fresh tissue can be sent to the microbiology laboratory in a sterile container to be processed for bacterial, fungal, or viral cultures. Tissue from patients with symptoms suggestive of spongiform encephalopathy (Creutzfeldt-Jakob disease) requires special handling. The infectious agent of Creutzfeldt-Jakob disease may be inactivated by immersing formalin-fixed tissue in 50 to 100 mL of pure formic acid for 1 hour, followed by reimmersion in fresh formalin.[11] While the clinical diagnosis of spongiform encephalopathy encompasses a spectrum of neurologic dysfunction, rapidly progressive dementia and myoclonus are especially suggestive of this diagnosis.[12]

If a lymphoproliferative disorder is suspected, a portion of fresh tissue can be sent to the surgical pathology laboratory, where it will be placed in appropriate holding media (RPMI) for flow cytometry. Refer to a previously published protocol for processing specimens from patients with non-Hodgkin lymphoma.[13]

Molecular diagnostic testing is playing an increasingly important role in the diagnosis, staging, and treatment of tumors.[14] Tissue that has been frozen shortly after arrival in the laboratory and stored at -70 [degrees] C will be suitable for these studies. Paraffin-embedded tissue can also occasionally be used.

G: Cytopathology: Histologic Type.--Tumor cells, especially those of glial lineage, are often altered by time in fluid/cerebrospinal fluid and are difficult to interpret unless cell clusters of tissue fragments are available. Choroid plexus and ependymal cells are quite similar, with the latter showing more "degenerative" cytologic features and fewer cellular clusters. Therefore, the designation choroidependymal cells is appropriate. Ependymomas and choroid plexus papillomas generally appear cytologically benign or bland. It is helpful to prepare squash preparations routinely during intraoperative consultations to develop or keep a sharp cytologic eye for CNS neoplasms.

H: Comments.--Correlation of clinical and radiographic information should be critically reviewed before final sign-out of the biopsy diagnosis.[15]

I: Histologic Type.--The World Health Organization (WHO) classification of tumors of the central nervous system is shown below.[16]

WHO Histologic Typing of Tumors of the Nervous System
TUMORS OF NEUROEPITHELIAL TISSUE
Astrocytic Tumors
Diffuse astrocytoma
 Fibrillary astrocytoma
 Protoplasmic astrocytoma
 Gemistocytic astrocytoma
Anaplastic astrocytoma
Glioblastoma
 Giant cell glioblastoma
 Gliosarcoma
Pilocytic astrocytoma
Pleomorphic astrocytoma
Pleomorphic xanthoastrocytoma
Subependymal giant cell astrocytoma

Oligodendroglial Tumors
Oligodendroglioma
 Anaplastic oligodendroglioma
Mixed gliomas
 Oligoastrocytoma
 Anaplastic oligoastrocytoma

Ependymal Tumors
Ependymoma
 Cellular
 Papillary
 Clear cell
 Tanycytic
Anaplastic ependymoma
Myxopapillary ependymoma
Subependymoma

Choroid Plexus Tumors
Choroid plexus papilloma
Choroid plexus carcinoma

Glial Tumors of Uncertain Origin
Astroblastoma
Gliomatosis cerebri
Chordoid glioma of the third ventricle

Neuronal and Mixed Neuronal-Glial Tumors
Gangliocytoma
Dysplastic gangliocytoma of cerebellum (Lhermitte-Duclos)
Desmoplastic infantile astrocytoma/ganglioglioma
Dysembryoplastic neuroepithelial tumor
Ganglioglioma
Anaplastic ganglioglioma
Central neurocytoma
Cerebellar liponeurocytoma
Paraganglioma of the filum terminale

Neuroblastic Tumors
Olfactory neuroblastoma (esthesioneuroblastoma)
Olfactory neuroepithelioma
Neuroblastomas of the adrenal gland and sympathetic
 nervous system

Pineal Parenchymal Tumors
Pineocytoma
Pineoblastoma
Pineal parenchymal tumor of intermediate differentiation

Embryonal Tumors
Medulloepithelioma
Ependymoblastoma
Medulloblastoma
 Desmoplastic medulloblastoma
 Large cell medulloblastoma
 Medullomyoblastoma
 Melanotic medulloblastoma
Supratentorial primitive neuroectodermal tumor
 Neuroblastoma
 Ganglioneuroblastoma
Atypical teratoid/rhabdoid tumor

TUMORS OF PERIPHERAL NERVES
Schwannoma (neurilemmoma, neurinoma)
 Cellular
 Plexiform
 Melanotic
Neurofibroma
 Plexiform
Perineurioma
 Intraneural perineurioma
 Soft tissue perineurioma

Malignant Peripheral Nerve Sheath Tumor
Epithelioid
Malignant peripheral nerve sheath tumor with divergent
 mesenchymal and/or epithelial differentiation
Melanotic
Melanotic psammomatous

TUMORS OF THE MENINGES
Tumors of Meningothelial Cells
Meningioma
 Meningothelial
 Fibrous (fibroblastic)
 Transitional (mixed)
 Psammomatous
 Angiomatous
 Microcystic
 Secretory
 Lymphoplasmacyte-rich
 Metaplastic
 Clear cell
 Chordoid
 Atypical
 Papillary
 Rhabdoid
 Anaplastic meningioma

Mesenchymal, Nonmeningothelial Tumors
Lipoma
Angiolipoma
Hibernoma
Liposarcoma (intracranial)
Solitary fibrous tumor
Fibrosarcoma
Malignant fibrous histiocytoma
Leiomyoma
Leiomyosarcoma
Rhabdomyoma
Rhabdomyosarcoma
Chondroma
Chondrosarcoma
Osteoma
Osteosarcoma
Osteochondroma
Hemangioma
Epithelioid hemangioendothelioma
Hemangiopericytoma
Angiosarcoma
Kaposi sarcoma

Primary Melanocytic Lesions
Diffuse melanocytosis
Melanocytoma
Malignant melanoma
Meningeal melanomatosis

Tumors of Uncertain Histogenesis
Hemangioblastoma

LYMPHOMAS AND HEMOPOIETIC NEOPLASMS
Malignant lymphomas
Plasmacytoma
Granulocytic sarcoma

GERM CELL TUMORS
Germinoma
Embryonal carcinoma
Yolk sac tumor (endodermal sinus tumor)
Choriocarcinoma
Teratoma
 Mature
 Immature
 Teratoma with malignant transformation
Mixed germ cell tumors

TUMORS OF THE SELLAR REGION
Craniopharyngioma
 Adamantinomatous
 Papillary
Granular cell tumor


METASTATIC TUMORS

J: Histologic Grade.--The WHO grading system (malignancy scale) of CNS tumors is shown below.[16] There is no formal TNM-based classification and staging system for the CNS at this time.[17]

After patient age, tumor histology and grade have been shown to be the strongest predictors of clinical course in selected CNS astrocytomas.[2,18] Several grading systems for diffusely infiltrating astrocytomas have been proposed, based on their ability to define distinct patient groups with significantly different survival curves. Both 3-tiered and 4-tiered systems are currently in use and have been reviewed.[19] Two examples of popular grading systems are shown below.[16] For a complete review and comparison of these systems, including the 3-tiered system such as the Ringertz system and modifications thereof, the reader is referred to the review by McClendon et al.[19]
 Grade Grade Grade Grade
Tumor Group Tumor Type I II III IV

Astrocytic Subependymal x
 tumors giant cell
 Pilocytic x
 Pleomorphic xan- x
 thoastrocytoma
 Low-grade x
 infiltrating
 Anaplastic x
 infiltrating
 Glioblastoma x
Oligodendro- Low-grade x
 gliomas Anaplastic x
Oligoastro- Low-grade x
 cytoma Anaplastic x
Ependymal Subependymoma x
 tumors Myxopapillary x
 Low-grade x
 Anaplastic x
Choroid Papilloma x
 plexus Carcinoma x x
 tumors
Neuronal/ Gangliocytoma x
 glial Ganglioglioma x x
 tumors Desmoplastic x
 infantile
 ganglioglioma
 Dysembryoplastic x
 neuroepithelial
 tumor
 Central x
 neurocytoma
Pineal Pineocytoma x
 tumors Pineocytoma/ x x
 pineoblastoma
 Pineoblastoma x
Embryonal Medulloblastoma x
 tumors Other primitive x
 neuroectodermal
 tumors
 Medulloepithelioma x
 Neuroblastoma x
 Ependymoblastoma x
Cranial Schwannoma x
 and nerve Malignant x x
 sheath peripheral nerve
 tumors sheath tumors
Meningeal Meningioma x
 tumors Atypical x
 meningioma
 Papillary x
 meningioma
 Anaplastic x
 meningioma
 Hemangiopericytoma x x


Comparison of the WHO and St. Anne/Mayo Grading Systems for Astrocytomas.[16]

WHO St. Anne/Mayo
Grade WHO Designation Designation Histologic Criteria

 I Pilocytic astrocytoma
 II Astrocytoma (low Astrocytoma, One criterion, usually
 grade) grade 2 nuclear atypia
III Anaplastic astrocy- Astrocytoma, Two criteria, usually
 toma grade 3 nuclear atypia and
 mitoses
 IV Glioblastoma multi- Astrocytoma, Three criteria,
 forme grade 4 usually nuclear
 atypia, mitoses, and
 endothelial
 proliferationi
 and/or necrosis


K: Other Pathologic Features.--Hemosiderin deposition, calcification, and microcyst formation are nonspecific findings that occur in both malignant and benign CNS neoplasms. However, in general, calcification usually favors a slowly growing neoplasm, which is more likely to be benign. The presence of gemistocytes, vascular proliferation, and necrosis represent negative prognostic indicators, and the latter 2 histologic changes are diagnostic of high-grade astrocytomas.[9,20-22]

Findings in Touch, Squash, or Scrape Preparations.--The presence of process-forming cells is suggestive of a primary CNS neoplasm. Extreme fibrillarity may represent reactive astrocytosis.[4(p39)] Touch or squash preparations are also of value in evaluating specimens for the presence of macrophages. A macrophage-rich lesion is more consistent with a subacute infarct or demyelinative lesion, rather than a tumor.

Local extension, rapid growth, invasion of adjacent structures, and CNS spread via the ventricular system or subarachnoid space are often suggestive of, but not always diagnostic of, malignancy. Low-grade neoplasms, such as meningioma and pilocytic astrocytoma, may also exhibit this type of spread, but at a slower rate of growth than most malignant tumors. Malignant and atypical meningeal tumors often invade brain substance.[24]

Members of the College of American Pathologists Neuropathology Committee contributed to the development of this protocol.

References

[1.] Lote K, Egeland T, Hager B, et al. Survival, prognostic factors, and therapeutic efficacy in low-grade glioma: a retrospective study in 379 patients. J Clin Oncol. 1997;15:3129-3140.

[2.] Wurschmidt F, Bunemann H, Heilmann HP. Prognostic factors in high-grade malignant glioma: a multivariate analysis of 76 cases with postoperative radiotherapy. Strahlenther Onkol. 1995;171:315-321.

[3.] Hirano H, Asakura T, Yokoyama S, et al. The prognostic factors in astrocytic tumors: analysis by the Kaplan-Meier method and the Weibull log-linear model. No Shinkei Geka. 1996;24:809-815.

[4.] Burger PC, Scheithauer B. Tumors of the Central Nervous System. Washington, DC: Armed Forces Institute of Pathology; 1994. Atlas of Tumor Pathology; 3rd series, fascicle 10.

[5]. Burger PC, Nelson JS. Stereotactic brain biopsies: specimen preparation and evaluation. Arch Pathol Lab Med. 1997;121:477-480.

[6.] Nitta T, Sato K. Prognostic implications of the extent of surgical resection in patients with intracranial malignant gliomas. Cancer. 1995;75:2727-2731.

[7.] Lantos PL, Vandenberg SR, Kleihues P. Tumors of the nervous system. In: Graham DI, Lantos PL, eds. Greenfield's Neuropathology. Vol 1. 6th ed. New York, NY: Oxford University Press; 1997:125-126, 586-587.

[8.] Jubelirer SJ. A review of the treatment and survival rates of 138 patients with glioblastoma multiforme. W V Med J. 1996;92:186-190.

[9.] Hammoud MA, Sawaya R, Shi W, Thall PF, Leeds NE. Prognostic significance of preoperative MRI scans in glioblastoma multiforme. J Neurooncol. 1996; 27:65-73.

[10.] Fischbein NJ, Prados MD, Wara W, Russo C, Edwards MS, Barkovich AJ. Radiologic classification of brain stem tumors: correlation of magnetic resonance imaging appearance with clinical outcome. Pediatr Neurosurg. 1996;24:9-23.

[11.] Rosenblum MK. Neuromuscular system. In: Rosai J, ed. Ackerman's Surgical Pathology. Vol 2. 8th ed. St Louis, Mo: Mosby-Year Book; 1996:2267-2268.

[12.] Prusiner SB, Bosque P. Prion diseases. In: Braunwald E, Fauci AS, Kasper DL, Hauser SL, Longo DL, Jameson JL, eds. Harrison's Principles of Internal Medicine. 15th ed. New York, NY: McGraw-Hill; 2001:2486-2491.

[13.] Compton CC, Harris NL, Ross DW, for the Cancer Committee, College of American Pathologists. Protocol for the examination of specimens from patients with non-Hodgkin's lymphoma: a basis for checklists. Arch Pathol Lab Med. 1999; 123:68-74.

[14.] Snijders AM, Meijer GA, Brakenhoff RH, van den Brule AJ, van Diest PJ. Microarray techniques in pathology: tool or toy? Mol Pathol. 2000;53:289-294.

[15.] Burger C, Scheithauer BW, Lee RR, O'Neill BP. An interdisciplinary approach to avoid the overtreatment of patients with central nervous system lesions. Cancer. 1997;80:2040-2046.

[16.] Kleihues P, Cavenee WK, eds. Pathology and Genetics of Tumors of the Nervous System: World Health Organization Classification of Tumors. Lyon, France: International Agency for Research on Cancer; 2000:6-7.

[17.] Fleming ID, Cooper JS, Henson DE, et al, eds. AJCC Cancer Staging Manual. 5th ed. Philadelphia, Pa: Lippincott-Raven; 1997:281-283.

[18.] Wakimoto H, Aoyagi M, Nakayama T, et al. Prognostic significance of Ki-67 labeling indices obtained using MIB-1 monoclonal antibody in patients with supratentorial astrocytomas. Cancer. 1996;77:373-380.

[19.] McLendon RE, Enterline DS, Tien RD, Thorstad WL, Bruner JM. Tumors of the central neuroepithelial origin. In: Bigner DD, McLendon RE, Bruner JM, eds. Russell and Rubinstein's Pathology of Tumors of the Nervous System. Vol 1. 6th ed. New York, NY: Oxford University Press; 1998:3117-314.

[20.] Watanabe K, Tachibana O, Yonekawa Y, Kleihues P, Ohgaki H. Role of gemistocytes in astrocytoma progression. Lab Invest. 1997;76:277-284.

[21.] Leon SP, Folkerth RD, Black PM. Microvessel density is a prognostic indicator for patients with astroglial brain tumors. Cancer. 1996;77:362-372.

[22.] Nelson JS, Tsukada Y, Schoenfeld D, Fulling K, Lamarche J, Peress N. Necrosis as a prognostic criterion in malignant supratentorial, astrocytic gliomas. Cancer. 1983;52:550-554.

[23.] McKeever PE, Burger PC, Nelson JS. Introduction to neurooncology. In: Nelson JS, Parisi JE, Schochet SS, eds. Principles and Practice of Neuropathology. St Louis, Mo: CV Mosby; 1993:109-122.

Bibliography

Bigner SH, Johnson WW. Cytopathology of the Central Nervous System. Chicago, III: American Society of Clinical Pathologists; 1994.

Bigner DD, McLendon RE, Bruner JM, eds. Russell and Rubinstein's Pathology of Tumors of the Nervous System. 6th ed. New York, NY: Oxford University Press; 1998.

Burger PC, Scheithauer B. Tumors of the Central Nervous System. Washington, DC: Armed Forces Institute of Pathology; 1994. Atlas of Tumor Pathology; 3rd series, fascicle 10.

Kleihues P, Cavenee WK, eds. Pathology and Genetics of Tumors of the Nervous System: World Health Organization Classification of Tumors. Lyon, France: International Agency for Research on Cancer; 2000.

Lantos PL, Vandenberg SR, Kleihues P. Tumors of the Nervous System. In: Graham DI, Lantos PL, eds. Greenfield's Neuropathology. Vol 2. 6th ed. New York, NY: Oxford University Press; 1997:583-879.

Accepted for publication April 19, 2001.

From the Department of Pathology, University of California--San Diego Medical Center (Dr Karpinski); the Department of Pathology, Deaconess Hospital, Oklahoma City, Okla (Dr Min); and Austin Pathology Associates, Austin, Tex (Dr Bauserman). Dr Karpinski is now with the Department of Pathology, Idaho Neurological Institute, Saint Alphonsus Regional Medical Center, Boise, Idaho.

This protocol was developed by the Cancer Committee of the College of American Pathologists and submitted for editorial review and publication. It represents the views of the Cancer Committee and is not the official policy of the College of American Pathologists.

Reprints: See Archives of Pathology & Laboratory Medicine Web site at www.cap.org.

Nancy C. Karpinski, MD; Kyung-Whan Min, MD; Steven C. Bauserman, MD; for the Members of the Cancer Committee, College of American Pathologists
COPYRIGHT 2001 College of American Pathologists
No portion of this article can be reproduced without the express written permission from the copyright holder.
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Author:Karpinski, Nancy C.; Min, Kyung-Whan; Bauserman, Steven C.
Publication:Archives of Pathology & Laboratory Medicine
Geographic Code:1USA
Date:Sep 1, 2001
Words:4233
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