Radiological Manifestations of Metastatic Melanoma

Radiological Manifestations of Metastatic Melanoma Lia Hojman, Universidad de Chile Year VII

Our patient: Clinical Presentation A 24 year old male. Former smoker. 8 months ago, he suffered a burn in his right hip while working. Then he noticed the area wasn t healing well and that a big, pigmented and raised mole appeared in the area where he noticed a mole a few years prior to the accident. 2

Our Patient: Melanoma local Management The biopsy showed a nodular melanoma with positive margins. He underwent a wide excision and inguinal + femoral lymphadenectomy. 3 3

Now that seen the local management of our patient s malignant melanoma, let s review some important aspects of melanoma 4 4

Risk Factors for Malignant Melanoma Risk factors: More than 100 moles in the entire body Familial history of melanoma Personal history of melanoma More than 4 atypical nevi Armstrong A, et al. Pathologic Characteristics of Melanoma in: UpToDate, Armstrong A. (Ed), UpToDate, Waltham, MA, 2008 5 5

Features of Suspicious Moles ABCDE of Moles: A for Assymetry B for irregular Borders C for Color variegation D fordiameter> 6 mm E for enlargement/ evolution 6 6

Let s check our patient s follow up studies 7 7

Our Patient: Right lower lobe nodule Right lower lobe pulmonary nodule, 1 cm in diameter Axial, C, Chest CT 8 PACS, BIDMC 8

Our Patient: Left lower lobe nodules Tiny submilimiter nodules in the lower segment of the left lower lobe Axial, C, Chest CT 9 PACS, BIDMC 9

Our Patient: Left lower lobe nodules Tiny submilimiter nodules in the lower segment of the left lower lobe Axial, C, Chest CT 10 PACS, BIDMC 10

Our Patient: Gastrohepatic lymph node mass Large conglomerate lymph node mass identified within the gastrohepatic ligaments Axial, C+, Abdominal CT 11 PACS, BIDMC 11

Our Patient: Hepatic Metastases There are metastasis in the liver. The largest measures 5.0 x 4.5 cm in segment II of the liver. And in the segment VII measuring 1.4 x 1.5 cm. Axial, C+, Abdominal CT 12 PACS, BIDMC 12

Our Patient: Hepatic Metastases There are metastasis in the liver. The largest measures 5.0 x 4.5 cm in segment II of the liver. And in the segment VII measuring 1.4 x 1.5 cm. He also was found to have metastasis in segments IVa and III. Axial, C+, Abdominal CT 13 PACS, BIDMC 13

Finding s Summary In the follow up CTs we found: Pulmonary Metastases Conglomerate lymph node mass in gastrohepatic ligament Liver Metastases 14 14

Metastasic Sites Where does melanoma spread to? Kumar R, et al. Clinical applications of fluorodeoxyglucose--positron emission tomography in 15 the management of malignant melanoma. Curr Opin Oncol. 2005 Mar;17(2):154-9. 15

Our patient: Further work up He underwent a Head MRI to see if there was also brain lesions. 16 16

Our Patient: Frontal Lobe nodule There is an approximately 1 cm enhancing mass within the right frontal lobe, which may lie within the cortex or could be sulcal, concerning for a metastatic lesion. Axial MR, T1 Flair PACS, BIDMC 17 17

Our Patient: Frontal Lobe nodule There is surrounding vasogenic edema within the right frontal lobe, though without mass effect or shift of midline. Axial MR, FLAIR sequence PACS, BIDMC 18 18

Our Patient: Temporal Lobe nodule Within the inferior left temporal lobe there is an enhancing lesion measuring approximately 3 mm without significant surrounding edema. Axial MR, Flair sequence PACS, BIDMC 19 19

Head MRI Findings Summary There is a 1 cm enhancing mass within the right frontal lobe, with surrounding vasogenic edema, concerning for metastatic lesion. In the left temporal node, a second enhancing lesion can be seen, without surrounding edema. 20 20

Our patient: Further work up To further characterize the lesions, a PET CT was performed. Butbeforeweseeourpatient spet CT, we are going to learn how a PET CT is done. 21 21

PET CT: The Pasteur Effect Glucose Glucose Aerobiosis O 2 Energy Energy In aerobiosis, glucose is transported into cells to be used in energy production. This is called Glycolysis In anaerobic conditions, the energy production process is less effective so there is enhanced uptake. This is called the Pasteur effect O 2 Anaerobiosis Stark P, et al. Computed Tomography and Positron Emission Tomographic 22 Scanning in: UpToDate, Stark P. (Ed), UpToDate, Waltham, MA, 2008. 22

PET CT: The Warburg Effect Glucose Glucose Normal Cell O 2 Tumor Cell In tumor, there is enhanced glycolysis even in aerobic conditions. This is called the Warburg effect. O 2 Stark P, et al. Computed Tomography and Positron Emission Tomographic Scanning in: UpToDate, 23 Stark P. (Ed), UpToDate, Waltham, MA, 2008. 23

PET CT: Changing Glucose for FDG Glucose FDG Physiologic Process Energy When we do a PET, we use a glucose analog, FDG, that can t be metabolized, so it stays in the cell. When it decays, emits protons that are sensed by the detectors. The more uptake, the darker it looks. Stark P, et al. Computed Tomography and Positron Emission Tomographic 24 Scanning in: UpToDate, Stark P. (Ed), UpToDate, Waltham, MA, 2008. 24

PET CT: The CT contribution Unfortunately, the PET by itself doesn t give enough anatomical information, but when is combined with a non contrast CT, we can see the anatomic position of a high FDG uptake focus. Axial, FDG, Chest PET PACS, BIDMC This test is normally used to look for metastases. Stark P, et al. Computed Tomography and PET Scanning in: UpToDate, Stark P. (Ed), UpToDate, Waltham, MA, 2008. 25 25

PET CT: The CT contribution Unfortunately, the PET by itself doesn t give enough anatomical information, but when is combined with a non contrast CT, we can see the anatomic position of a high FDG uptake focus. Axial, FDG, Chest PET PACS, BIDMC Axial, FDG, Chest PET PACS, BIDMC Axial, C, Chest CT This test is normally used to look for metastases. 26 Stark P, et al. Computed Tomography and PET Scanning in: UpToDate, Stark P. (Ed), UpToDate, Waltham, MA, 2008. 26

PET CT: It s not perfect Sources of error: False positive High uptake due to active infections. High uptake due to brown fat. False negative Tumors with low metabolic activity Too small tumors (less than 7 mm in diameter) Hyperglicemia: Glucose and FDG compete for the same receptors. Stark P, et al. Computed Tomography and PET Scanning in: UpToDate, Stark P. (Ed), UpToDate, Waltham, MA, 2008. 27 27

Follow up PET So now that we understand how it works, let s see what we find 28 28

Our Patient: Subcarinal lymph node conglomerate PACS, BIDMC Axial, FDG, Chest PET Axial, C, CT Axial, FDG, Chest PET Axial, FDG, Chest CT CHEST: A 2.2 cm subcarinal lymph node conglomerate to the right of midline, with increased uptake with SUV max of 6.6. The previously seen right lower lobe nodule near the diaphragm measures 1.5 cm and demonstrates minimal avidity with SUV max 2.1. 29 29

Our Patient: Liver Mets and Lymph node conglomerate PACS, BIDMC Axial, FDG, Chest PET Axial, C, CT Axial, FDG, Chest PET Axial, FDG, Chest CT Extensive diffuse FDG avidity is seen in the liver,predominantly in the left lobe. Also involving the periportal tissue, IVC and aorta, corresponding to regions of known liver metastases and lymph node conglomerates. 30 30

Our Patient: Vertebral C5 early metastasis PACS, BIDMC Axial, FDG, Chest PET Axial, C, CT Axial, FDG, Chest PET Axial, FDG, Chest CT A focus of FDG tracer uptake is seen in the vertebral body of C5 with SUV max 3.6. It has no correlation in CT Concerning for early metastasis. 31 31

PET CT Findings Summary Focus of FDG tracer uptake was seen in Subcarinal lymph node conglomerate The liver, predominantly in the left lobe. The vertebral body of C5 32 32

PET CT Findings Summary Focus of FDG tracer uptake was seen in Subcarinal lymph node conglomerate The liver, predominantly in the left lobe. The vertebral body of C5 Next, we will review some basic facts on bone metastases 33 33

Bone Metastasis Metastasis are the most common variety of bone tumor Always consider them in an older patient. The most common primary tumors are Greenspan, Adam. Differential diagnosis of tumor and tumor like lesions of bones and joints. First Edition. New York, 34 NY. Editorial Lippincott Raven; 1998 34

Bone Metastasis: Most common primary tumors Thyroid Breast Lung Kidney Prostate Uterus Also gastric cancer, colon, urinary, melanoma 35 Greenspan, Adam. Differential diagnosis of tumor and tumor like lesions of bones and joints. First Edition. New York, 35 NY. Editorial Lippincott Raven; 1998 35

Bone Metastasis: Favorite Localizations Axial skeleton Proximal parts of limbs Greenspan, Adam. Differential diagnosis of tumor and tumor like lesions of bones and joints. First Edition. New York, 36 NY. Editorial Lippincott Raven; 1998 36

Bone Metastasis: Favorite Localizations Axial skeleton Proximal parts of limbs Greenspan, Adam. Differential diagnosis of tumor and tumor like lesions of bones and joints. First Edition. New York, 37 NY. Editorial Lippincott Raven; 1998 37

Bone Metastases: Lytic vs Blastic Lytic lesions represent ~ 75% : Blastic lesions represent ~ 15% : Kidney Lung Breast GI tract Thyroid Prostate Seminoma Breast Cervix Ovary Mixed Lesions: Represent 15%. Most common are Breast and Lung Greenspan, Adam. Differential diagnosis of tumor and tumor like lesions of bones and joints. First Edition. New York, 38 NY. Editorial Lippincott Raven; 1998 38

Companion Patient 1: An example of lytic metastasis of Renal Carcinoma Courtesy of Dr. Corrie Yablon 39 Axillary projection, Shoulder Plain Film PACS, BIDMC 39

Companion Patient 1: An example of lytic metastasis of Renal Carcinoma Expansile lytic ovoid destructive lesion at the periphery of the proximal humerus. Destroying and scalloping the underlying bone with an associated soft tissue mass. Courtesy of Dr. Corrie Yablon Axillary projection, Shoulder Plain Film 40 PACS, BIDMC 40

Companion Patient 2: An example of mixed metastases of Breast Cancer Sagittal, C, Spinal CT PACS, BIDMC Courtesy of Dr. Corrie Yablon 41 41

Companion Patient 2: An example of mixed metastases of Breast Cancer Blastic Lesion in body of T12 Sagittal, C, Spinal CT PACS, BIDMC Courtesy of Dr. Corrie Yablon 42 42

Our Patient: Treatment choices and Prognosis Poor prognosis: Melanoma stage IV with brain metastases. Plan: Brain Metastaes: Stereotactic Surgery Quimiotherapic treatment: Temozolomide Alkylating agent Bonds to Guanine in DNA DNA damage Cell death Ipilimumab remains as an alternative Monoclonal antibody Targeted against CTL4, antigen that works as an inhibitor of T cell actvity. Ipilimumab blocks the inhibitor, resulting in T cell stimulation T cells recognize and attack the tumor. 43 43

Summary of the presentation In this presentation, we have reviewed: History of a patient with metastasic melanoma Risk factors for melanoma ABCDE of moles Metastasic melanoma on a Chest CT Metastasic melanoma on an Abdominal CT Frequent locations of melanoma metastases Metastasic melanoma on Head MRI How a PET CT works Pasteur effect Warburg effect 44 44

Ipilimumab 45 45 Lia Hojman, VII Summary of the presentation 2 How a PET CT works FDG and its difference with glucose The CT contribution Sources of error False Positive False Negative Metastasic Melanoma on PET CT Bone Metastases General Aspects Most common Primary Tumors Favorite localizations Lytic vs Blastic Lesions Stage IV Melanoma Treatment: Temozolomide

Acknowledgments Corrie Yablon, MD Emily Hanson, Student Coordinator Seth Berkowitz, MD Claudio Karsulovic, MS4 Jim Brophy, PACS 46 46

References Dancey AL, et al. A review of diagnostic imaging in melanoma. J Plast Reconstr Aesthet Surg. 2008 Nov;61(11):1275 83 Greenspan, Adam. Differential diagnosis of tumor and tumor like lesions of bones and joints. First Edition. New York, NY. Editorial Lippincott Raven; 1998 El Maraghi RH, et al. PET vs sentinel lymph node biopsy for staging melanoma: a patient intervention, comparison, outcome analysis. J Am Coll Radiol. 2008 Aug;5(8):924 31. Vandewoude M, et al. (18)FDG PET scan in staging of primary malignant melanoma of the esophagus: a case report. Acta Gastroenterol Belg. 2006 Jan Mar;69(1):12 4. Kumar R, et al. Clinical applications of fluorodeoxyglucose positron emission tomography in the management of malignant melanoma. Curr Opin Oncol. 2005 Mar;17(2):154 9. Stone M, et al. Evaluation and Treatment of regional Lymph nodes in Melanoma in: UpToDate, Stone M. (Ed), UpToDate, Waltham, MA, 2009. Armstrong A, et al. Pathologic Characteristics of Melanoma in: UpToDate, Armstrong A. (Ed), UpToDate, Waltham, MA, 2008. Stark P, et al. Computed Tomography and Positron Emission Tomographic Scanning in: UpToDate, Stark P. (Ed), UpToDate, Waltham, MA, 2008. 47 47