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The utility of thyroglobulin

This is an example of the utility of thyroglobulin. This is a patient who had surgery and 131 iodine ablation over here. The thyroglobulin level was initially around 5 at the time they were off suppression. They were started on thyroxin suppression. Their TSH was brought low and their thyroglobulin declined. A year later their thyroxin was stopped, TSH went back up, there was a slight increase in the thyroglobulin levels but the 131 iodine scan was negative, so they were put back on suppression. Several months after that their thyroglobulin, even while on suppression, started to rise and then when they were taken off suppression there was a considerably greater increment in their thyroglobulin, and the scan at that time was positive showing recurrent disease with pulmonary mets, which was treated with a second treatment with radioiodine.

Finally, as far as the other treatment issue that is available is the question of what one should do as far as thyroxine suppression. This is just some data from a recent, retrospective study, in which patients were scaled regarding the degree of thyroxine suppression. There were some patients who had essentially undetectable TSH’s and other patients whose TSH was not quite fully suppressed. What this is showing is that in patients with – this is going back to a TNM staging – TNM stage I or II disease, that there was not very much of an impact on recurrence related to the degree of thyroxin suppression but that in these higher risk patients with stage III disease, particularly, that the patients who were more fully suppressed had a lower risk of recurrence. So again, certainly in some of the patients who might be at a higher a priori risk there’s justification in treating them with sufficient thyroxine to keep their TSH suppressed, I feel that to an undetectable level at least for the first several years after treatment.

What about the patients who, in a way, I suppose you might be more likely to see, or the ones we need to call for additional help on, are those with differentiated radioiodine resistant thyroid cancer. A couple of potential treatment options; there is a role for external beam irradiation in these patients.

Chemotherapy has been, I’d say, disappointing at best, but there still may be a role for it. The most commonly used drug has been Adriamycin, either by itself or in combination with cisplatin, with other agents. There are a variety of kind of interesting approaches being tried right now. In addition I believe there is a Taxol trial going on, although I haven’t seen any results on it. There has also been this interest in redifferentiation, in trying to treat the tumor in such a way as to lessen its radioiodine resistance and enable it to be more effective in taking up radioiodine. Retinoic acid and its congeners has been used and there has also been this interesting finding that occasionally in patients treated with Adriamycin as chemotherapy, that if you repeat the scan after they have gone through a couple of treatment cycles, that there have been some patients who have then been shown to take up radioiodine.

Suggesting that in some way there was some type of redifferentiation that took place. But clearly, these patients who get to a stage of radioresistant disease are a very very troubling group to treat.

My approach, in terms of these patients, is; the question is whether they have progressive disease and whether they are symptomatic. If they are not symptomatic – and many many patients, even with extensive thyroid cancer, may not be – or maybe minimally symptomatic, there is certainly reason to simply continue to follow those patients. If there are significant symptoms taking place, which may frequently relate to bony metastases, then I think the important issue is to localize the disease. If the disease if very focal, if it involves an isolated or bony matter or a large soft tissue lesion, then there is certainly a role for external beam irradiation and/or surgery, depending on the locations involved. If the patient is progressing, has diffuse disease, then I think that might be the situation in which there would be a role for systemic chemotherapy, using either Adriamycin or some combination of agents. Then as I mentioned, consider at least not giving up totally on radioiodine but consider another scan maybe after a few cycles to see if there might have been some redifferentiation issue.

Common brain tumors


Lung (37) Meningioma (80) Glioblastoma (47)
Breast (19) Acoustic neuroma (10) Anaplastic astrocytoma (24)
Melanoma (16) Pituitary adenoma (7) Astrocytoma (15)
Colorectum (9) Other (3) Oligodendroglioma (5)
Kidney (8) Lymphoma (2)
Other (11) Other (7)

These figures, given in parentheses, can be extremely variable from one center to another, depending on referral pattern. They are given here as general estimates based upon many published series.


A. Astrocytic tumors
1. Astrocytoma
2. Pilocytic
3. Subependymal
giant cell astrocytoma (ventricular tumor or tuberous sclerosis)
4. Astroblastoma
5. Anaplastic
(malignant) astrocytoma
B. Oligodendroglial tumors
2. Mixed
3. Anaplastic
(malignant) oligodendroglioma
C. Ependymal and choroid plexus
a.Myxopapillary ependymoma
b.Papillary ependymoma
2. Anaplastic
(malignant) ependymoma
3. Choroid plexus
4. Anaplastic
(malignant) choroid plexus papilloma
D. Pineal cell tumor
1. Pineocytoma (pinealcytoma)
2. Pineoblastoma (pinealoblastoma)
E. Neuronal tumors
1. Gangliocytoma
2. Ganglioglioma
4. Anaplastic
(malignant) gangliocytoma and ganglioglioma
5. Neuroblastoma
F. Poorly differentiated and
embryonal tumors
1. Glioblastoma
a.Glioblastoma with sarcomatous component (mixed glioblastoma and sarcoma)
b.Giant cell glioblastoma
2. Medulloblastoma
a.Desmoplastic medulloblastoma
4. Primitive polar
5. Gliomatosis

This is one of several formal schemes that are based on neuropathologic criteria. Metastasis is not considered, and one can get no sense of a given tumor as a clinical problem, as suggested by the simple classification in previous table.

Brain Tumors

More than 18,000 new cases of primary brain tumors are treated each year in the United States. Metastases are even more frequent and contribute considerably to suffering and death from systemic cancer. The diversity of brain tumors makes it important to attend to what is characteristic about each histologic type. Biologic specificity guides therapy to some extent now, and will be the key to successful treatment in the future.

The classification of brain tumors is a subject with confusing terminology. This text employs the simple approach of classifying brain tumors into metastatic, primary extra-axial, and primary intra-axial . These categories include all of the primary brain tumors listed in the World Health Organization classification , and adds pituitary and metastatic tumors. Although obviously simple, it follows practical clinical thinking. This chapter deals with the general biology, clinical features, and treatment of brain tumors as an overall problem.


“Is it benign or malignant?” is invariably the first question asked by patients, families, and physicians when confronted with a diagnosis of brain tumor. About a third of primary brain tumors can be called benign. Meningiomas and acoustic neuromas are good examples. They grow slowly, often can be removed completely, and rarely recur.

The concept of malignancy in the central nervous system (CNS) has a different meaning from that which applies to systemic cancers. The term “malignant” has nothing to do with metastasis out of the CNS, which is extraordinarily rare. It has everything to do with anatomic location and the possibility of complete surgical removal. Unless a tumor can be completely excised to the last cell, all intracranial neoplasms are potentially malignant in that they may recur, and often do.

Cerebral edema

Cerebral edema is an increase in brain volume caused by an absolute increase in cerebral tissue water content.Diffuse cerebral edema may develop soon after head injury. Vasogenic edema arises from transvascular leakage caused by mechanical failure of the tight endothelial junctions of the BBB. Vasogenic edema is frequently associated with focal contusions or hematomas. It eventually resolves as edema fluid is reabsorbed into the vascular space or the ventricular system.

Cytotoxic edema is an intracellular process that results from membrane pump failure. It is very common after head injury and is frequently associated with posttraumatic ischemia and tissue hypoxia. Normal membrane pump activity depends on adequate CBF to ensure adequate substrate and oxygen delivery to brain tissue. If the CBF is reduced to 40% or less of baseline, cytotoxic edema begins to develop. If CBF drops to 25% of baseline, membrane pumps fail and cells begin to die. Congestive brain swelling can contribute to cytotoxic edema if it becomes severe enough to increase ICP and reduce CPP so that cerebral circulation cannot be maintained.

Alteration in Consciousness

Consciousness is a state of awareness of the self and of the environment and requires intact functioning of the cerebral cortices and the reticular activating system (RAS) of the brain stem. An altered level of consciousness is the hallmark of brain insult from any cause and results from an interruption of the RAS or a global event that affects both cortices.

A patient who has sustained TBI commonly has an altered level of consciousness. Head-injured patients may be hypoxic from injury to respiratory centers or from concomitant pulmonary injury. Hypotension from other associated injuries can compromise CBF and affect consciousness. Global suppression may be present as a result of an intoxicating substance consumed before the injury. With increasing ICP from brain swelling or an expanding mass lesion, brain stem compression and subsequent RAS compression can occur.

Patients with altered levels of consciousness require careful monitoring and observation. Reversible conditions that can alter mental status, such as hypoxia, hypotension, hypoglycemia, should be corrected as they are identified.

Primary CNS lymphoma relative to chemotherapy

Just to give you an idea of what types of responses you can have. This is a 52-year-old man, presented with a huge mass in his right temporal parietal lobe. This was found on biopsy to be a CNS lymphoma and after two cycles on a regimen that we use, consisting of high dose methotrexate, cyclophosphamide and vincristine, after two cycles this was his scan.

This is before radiation therapy. So again a very satisfying disease to treat.

There remain a number of questions of primary CNS lymphoma relative to chemotherapy, such as who benefits from chemotherapy? We talked about the issue of immunocompetent versus immunodeficient patients. Prognostic factors seem to make a difference, with age being the most important. That elderly patients do not tolerate the chemotherapy as well or they don’t tolerate the chemotherapy side effects, and indeed they do not appear to benefit as much as younger patients. But what the age cut-off is and why this should be the case remains totally unknown. Issues relative to performance status, pathology and extent of disease appear to be less significant, at least for immunocompetent patients being treated with chemotherapy. There also continue to be significant and growing questions about the appropriate role for radiotherapy, such as what is the optimal dose and fractionation scheme, since combining chemotherapy and radiation now patients are living longer, one begins to have to worry about long term neuro-cognitive sequelae. One is beginning to question, with optimal chemotherapy, does one even need to use radiation therapy. So these are questions that still remain outstanding in primary CNS lymphoma. Again, a difficult problem in answering these questions given the relative rarity of the disease.

I’d like to just finish up by talking a little bit about, and mentioning a few of the recent developments, in the treatment of brain metastasis. A problem that medical oncologists obviously see quite frequently. The reason for that is that 20-40% of all cancer patients will develop brain metastases, accounting for 170,000 cases per year. The majority of these patients have lung cancer. Most of the metastases occur in the gray white matter, of which 80% is supratentorial. The few tumor types that can metastasize to the dura are breast and prostate, while the two tumor types that appear as hyperdense lesions without contrast are renal cell carcinoma, melanoma and actually sarcoma. But most of the other metastases appearing as hypo or iso-dense lesions.

Histopathologic examination of basal cell epitheliomas

Histopathologic examination of basal cell epitheliomas reveals collections of cells with dark-staining nuclei and scant cytoplasm. The periphery of the cell masses shows cells in a palisade arrangement resembling the basal layer of the epidermis. Treatment of basal cell epitheliomas consists of complete surgical excision, destruction by curettage and electrodesiccation, or radiation therapy. Cryosurgery has been employed for selected lesions, especially superficial basal cell carcinomas. A margin of seemingly normal tissue should be removed around the tumor to prevent recurrence arising from invasion by strands of tumor cells. The clean margins must be monitored by histopathologic examination.

Recurrent basal cell carcinomas are usually difficult to cure, but Mohs’ microscopic controlled surgery, when it is performed by a specially trained physician, is effective in eradicating the entire tumor. Routine in vivo chemosurgical fixation of the tumor with zinc
chloride paste is no longer required. In the current procedure, fresh tissue is removed after local anesthesia, and frozen sections are examined microscopically. This more efficient method spares a larger amount of normal skin and reduces the discomfort associated with chemical fixation. The tumor is removed layer by layer, and all margins are carefully examined until a tumor-free plane is achieved.

Indications for microscopic controlled excision of skin cancer include recurrent basal cell epitheliomas and squamous cell carcinomas; tumors with indistinct margins, such as sclerosing basal cell epitheliomas; and lesions in such areas as the inner and outer canthus of the eye and the tip of the nose, where maximal preservation of normal skin is desirable. For certain complicated or advanced tumors, the fixed-tissue approach is considered more reliable than the fresh-tissue technique.