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Paraneoplastic Endocrinopathies – Carcinogenesis

by Carlo Raj, MD
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    00:01 Other important paraneoplastics. And here, these are paraneoplastic endocrinopathies associated with cancer. Here we have Cushing's.

    00:10 When we talk about Cushing's we will have four different causes. With Cushing's syndrome, you could have what's known as, the most common, iatrogenic, injection. Lot's of people taking prednisone and cortisone for different reasons. Pain, cancer, donor recipient so on and so forth. Number 2, ACTH independant cause of hypercortisolism, adrenal cortex. Number 3, anterior pituitary, Cushing's disease. Number 4, from the lung ectopic production of ACTH. Here is small cell lung cancer, number two.

    00:55 The first time we saw small cell and paraneoplastic I talked to you about Eaton-Lambert. Here we have ACTH. What's your patient look like? Cushing's. Moon facies, buffalo hump, wasted extremities, truncal obesity, so on and so forth. Gynecomastia. Here you are thinking about choriocarcinoma. I will tell you this much. Chorio means placenta. However you can have choriocarcinoma that is going to be either gestational or non-gestational. Gestational choriocarcinoma you should be thinking about the entire placenta in which all the villi had been affected. What villi? The chorionic villi. You are going to produce a lot of Hcg.

    01:35 Or choriocarcinoma may be perhaps in the gonads, okay. Two different places with choriocarcinoma. In case you are confused, not to worry.

    01:43 We'll organize it exactly as such. Hcg, gynecomastia. Hypercalcemia, what kind of paraneoplastic issue migh you find with this? SCC, RCC.

    01:56 And both of this types of cancers paraneoplastically you might increase the levels of Pth-RP, related peptide. What does this do? It behaves just like Pth but it's not Pth. It's the scoundrel cousin who comes in and increases hypercalcemia whereas Pth levels will actually drop in your patient. Do not forget that. There is a big time difference between a related peptide paraneoplastically, versus that which is being produced endogeneously by the parathyroids. All that I with to say about this topic here, do not focus upon hypocalcemia. Your focus should be on medullary cancer of the thyroid and the fact that it paraneoplastically, through your parafollicular C cells, will produce calcitonin of the thyroid. Here is my third and final paraneoplastic with small cell in our table.

    02:53 Small cell first time we saw it paraneoplastically you should be thinking about Eaton-Lambert myasthenic syndrome.

    02:58 Number 2, small cell, we talked about ectopic production of ACTH. Small cell ectopically will be producing ADH. Therefore with all this antidiuretic hormone working upon your V2 receptors is then going to reabsorb your water. Your urine is going to be ridiculously high osmolarity. So you increased urine osmolarity. Resulting in hyponatremia. Then we have polycythemia. You will notice here that we are not calling this, or I am not calling this polycythemia vera. What's the reason for that? Paraneoplastically, you have RCC, or maybe perhaps HCC. Renal cell carcinoma or hepatocellular carcinoma which paraneoplastically will produce Epo, erythropoietin.

    03:44 All this erythropoietin which is then being produced will absolutely inappropriately stimulate the bone marrow to produce RBC's only.

    03:56 And therefore produce what kind of polycythemia? Primary or secondary polycythemia? Now be very careful. Students get this confused.

    04:04 Because they see cancer they think "Oh this must be primary polycythemia". That could not be further from the truth.

    04:11 These are cancers that are located apart from the bone marrow either the liver or the kidney producing erythropoietin. Therefore bringing about primary polycythemia. As a rule of thumb, if you find increase Epo and increase RBC mass, secondary polycythemia.

    04:29 Other examples, hypoxia or blood doping. Welcome to Lance Armstrong. We'll talk about that later. Primary polycythemia would be a tumor located where? In the bone marrow shutting down my Epo. Important tumor markers that you want to be familiar with.

    04:48 An increase in alpha feto-protein. HCC, Yolk Sac tumor. When would you find yolk sac tumor? Your child less than 5 years of age.

    04:59 Most common cause of gonadal cancers. Most common cause of testicular tumor in a boy less than 5. Yolk sac. Most common cause of ovarian tumor in a girl less than 5. Yolk sac. Look for increased alpha feto-protein. Bence Jones proteins, what are these? These are light chains that you would find with either multiple myeloma which is producing; Be careful, don't let the M's fool you.

    05:26 Multiple myeloma is not producing IgM. That will be Waldenstrom. Multiple myeloma will be producing either IgG or IgA.

    05:35 Waldenstrom is producing IgM. In other case, with all this immunoglobulins that are being secreted, it is light chains that you are worried about with Bence-Jones proteins. Kappa increased much more so than lambda. Remember those are your light chains.

    05:53 These are called Bence-Jones proteins. How would you go about staining this? Congo red. And what kind of stain or when would you use Congo red stain? Good. Amyloid, that's what this is. Ca-125 you should be thinking about surface derived ovarian tumor.

    06:12 What's the most common malignant ovarian tumor please? Serous cystadenocarcinoma. Why did we talk about that before? Seeding. Cea, carcinoembryonic antigen. And for this colorectal and maybe perhaps pancreas.

    06:33 Psa, on your boards, you should be thinking about prostate cancer.


    About the Lecture

    The lecture Paraneoplastic Endocrinopathies – Carcinogenesis by Carlo Raj, MD is from the course Cellular Pathology: Basic Principles.


    Included Quiz Questions

    1. Renal cell carcinoma causing ectopic production of ACTH
    2. Iatrogenic
    3. Small cell lung cancer causing ectopic production of ACTH
    4. ACTH independent hypercortisolism due to hyperactive adrenal cortex
    5. Cushing's disease of the anterior pituitary
    1. HCG
    2. ACTH
    3. ADH
    4. PTH-related peptide
    5. Calcitonin
    1. Multiple Myeloma
    2. Small cell lung cancer
    3. Colorectal cancer
    4. Prostate cancer
    5. Renal cell carcinoma
    1. Male gender
    2. Female gender
    3. Male or female over the age of 60
    4. Children under the age of 5
    5. Pregnant female

    Author of lecture Paraneoplastic Endocrinopathies – Carcinogenesis

     Carlo Raj, MD

    Carlo Raj, MD


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