Medullary Thyroid Cancer

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  • Hip/pelvis series : blastic and lytic bony lesions in pelvis and proximal femurs, more extensive in right femur than left, with soft tissue swelling over right greater trochanter. No definite fracture-line.
  • CBC : WBC 8.8 diff 92N , Hct/Hb 41.1/14.0, Plt 245, MCV 102.8 BMP : Na 134, K 4.5, Cl 95, CO2 22.6 , BUN 39 , Cr 2.0 , Glc 97, Ca 9.6, P 4.0, Mg 2.0; AG = 16.4 ; corrected serum Ca = 10.1 LFT : Tprot 7.9, Alb 3.4, Tbili 0.5, AST 26, ALT 26, AlkPhos 61 , LDH 143 ; protein gap = 4.5 Coags : PT 13.9, INR 1.1, PTT 31.4 Cardiac : CK 394 , CKMB 2.3, TrpI <0.04 Urine : trace protein , small blood , no RBCs, few bacteria , otherwise negative CEA : 198.6
  • “ Although some tumors may produce mainly osteolytic lesions (eg kidney cancer) and others mainly osteoblastic lesions (eg prostate cancer), most metastatic lesions produce both types of lesion and may go through stages where one or the other predominates.” (Harrison’s 628)
  • CT Abdomen/Pelvis: Numerous hypodense lesions in the liver, too small to characterize Pancreas, adrenal glands, spleen, and bowel are unremarkable No retroperitoneal adenopathy or pelvic mass/adenopathy Numerous sclerotic lesions in vertebral bodies a nd pelvis, consistent with metastatic disease Lytic lesion of right proximal femur with pathologic fracture Bone Scan: Demonstrates foci of increased tracer uptake as well as areas of absent uptake throughout pelvis and proximal femurs bilaterally, consistent with lytic and blastic nature of lesions.
  • 97% of MEN-2A, 95% of MEN-2B, and 86% of FMTC have mutations of the RET proto-oncogene on chr 10 Mutations of RET have been identified in sporadic MTC as well
  • In MTC, CEA doubling time of <1 yr has been associated with rapidly progressive disease (Saad et al, 1984)
  • Medullary Thyroid Cancer

    1. 1. Limping toward a diagnosis: A work-up of non-traumatic hip pain Presented by Travis Baggett Baylor College of Medicine Faculty Mentor: Dr Ed Young
    2. 2. Patient Profile and Chief Complaint: <ul><li>A 66yo Caucasian male with Chronic Renal Insufficiency, COPD, and a 100 pack-year history of smoking presents with a chief complaint of: </li></ul><ul><li>“ I have severe right hip pain.” </li></ul>
    3. 3. History of Present Illness <ul><li>Onset 4 weeks ago </li></ul><ul><li>Constant, worsening , rated 10/10 </li></ul><ul><li>Refractory to Tylenol #3, Percocet, and Methadone </li></ul><ul><li>Associated with right leg swelling </li></ul><ul><li>Worsened by movement </li></ul><ul><li>Denies history of trauma </li></ul><ul><li>Unable to walk or bear weight, uses wheelchair </li></ul>
    4. 4. Pertinent Review of Systems <ul><li>Reports weight loss of ~25lbs over past 2-3 months, and decreased appetite with early satiety </li></ul><ul><li>Also reports some urinary symptoms including hesitancy, intermittency, and incomplete voiding </li></ul><ul><li>Denies any other symptoms </li></ul>
    5. 5. Other History <ul><li>Past Medical and Surgical History: </li></ul><ul><li>COPD </li></ul><ul><li>Chronic Renal Insufficiency </li></ul><ul><li>Epidermal Inclusion Cysts </li></ul>Medications: Methadone, Percocet, Tylenol #3, COPD inhalers Allergies: NKDA
    6. 6. Other History <ul><li>Family History: </li></ul><ul><li>Father - cancer of unknown type/site </li></ul>Social History: Lives alone, has not worked since 1992. Denies any known toxin exposure or contacts with TB. Habits: -Smoking: 2ppd x 50yrs -EtOH: heavy use until 1992 -No illicit drug use
    7. 7. Physical Exam <ul><li>Vitals: BP 171/76, HR 109 , RR 20, T 96.6 F </li></ul><ul><li>Gen: cachectic </li></ul><ul><li>HEENT: sclera anicteric, bitemporal wasting </li></ul><ul><li>Neck: no LAN, palpable masses, or thyromegaly </li></ul><ul><li>Heart: tachycardic, otherwise normal </li></ul><ul><li>Lungs: tachypnic, occasional ronchi, hyperresonant </li></ul><ul><li>Chest: no breast masses </li></ul><ul><li>Abd: NT/ND, no HSM, no masses </li></ul><ul><li>Rectal: pt refused </li></ul>
    8. 8. Physical Exam (cont.) <ul><li>Extr: swelling/mass in R hip area with marked tenderness; no inguinal LAN; atrophy of BLE, R>L; RLE grossly shorter than LLE with poor ROM; 2+ pitting edema up to R mid-shin </li></ul><ul><li>Neuromuscular: generally weak , strength 1/5 in proximal RLE due to pain ; sensation diminished to light touch over R shin; DTR 3+ at R patella </li></ul><ul><li>Skin: no jaundice or suspicious lesions </li></ul>
    9. 9. Hip/Pelvis Film one week prior to admission
    10. 10. Other prior work-up <ul><li>For unclear reasons, two carcinoembryonic antigen (CEA) levels had been drawn over the past four years and were found to be elevated (nl = 0-5): </li></ul>CEA = 115 in 1998 CEA = 46 in 2000 <ul><li>No official record of prior sigmoidoscopy or colonoscopy </li></ul><ul><li>Pt reports having “normal” lower GI scope 10 yrs ago </li></ul>
    11. 11. Admission Labs <ul><li>CBC : diff 92N, MCV 102.8 </li></ul><ul><li>BMP : Cl 95, AG=16, BUN 39, Cr 2.0; corrected Ca WNL </li></ul><ul><li>LFT : TP 7.9, Alb 3.4, protein gap=4.5, AlkPhos WNL </li></ul><ul><li>Urine : tr protein, few bacteria, no RBCs </li></ul>Admission Studies Portable chest film: COPD, blunting of right costophrenic angle, and a small nodular density in the left midlung, all unchanged from previous studies. PSA = 0.58 TSH = 1.7 CEA = 199
    12. 12. Preliminary considerations… <ul><li>Malignancy </li></ul><ul><li>2) Malignancy </li></ul><ul><li>3) Malignancy </li></ul>
    13. 13. 1) Metastatic malignancy <ul><li>Lung cancer : 100 pack-year h/o smoking, chest film with suspicious but nonspecific changes; no hemoptysis or cough </li></ul><ul><li>Prostate cancer : pt with obstructive urinary symptoms but refuses rectal exam; PSA is WNL but this may be compatible with advanced disease </li></ul><ul><li>Thyroid cancer : no palpable neck masses, no cervical LAN, no vocal changes; TSH is WNL but this does not rule out disease </li></ul><ul><li>Kidney cancer : h/o smoking, but no hematuria, abdominal pain, or palpable flank masses </li></ul><ul><li>Bladder cancer : h/o smoking, but no hematuria or irritative symptoms </li></ul>
    14. 14. More on metastatic malignancy… <ul><li>Breast cancer : no palpable breast masses on exam; rare in males </li></ul><ul><li>Colorectal cancer : GUAIAC status unknown; denies any GI symptoms; ?CEA </li></ul><ul><li>Liver cancer : h/o EtOH abuse, but no evidence of liver disease and no abdominal pain/mass; LFTs are WNL; ?CEA </li></ul><ul><li>Pancreatic cancer : h/o smoking with recent weight loss, but no abdominal pain, jaundice, or h/o pancreatitis; rare bone involvement; ?CEA </li></ul>
    15. 15. 2) Hematologic malignancy <ul><li>Multiple myeloma : bone pain worse with movement, protein gap, and renal insufficiency, but no marked hypercalcemia, no anemia; typically little or no osteoblastic activity in MM </li></ul><ul><li>Lymphoma : weight loss but no fevers, sweats, LAN, or lymphocytosis </li></ul><ul><li>Leukemia : no anemia, neutropenia, thrombocytopenia, or hepatosplenomegaly </li></ul>
    16. 16. 3) Primary malignancy and others <ul><li>Bone or soft tissue sarcomas : suggested by possible hip mass on exam and bony lesions on x-ray, but normal AlkPhos and Ca levels; extremely rare and less likely </li></ul><ul><li>Gardner’s Syndrome : bone tumors + epidermal inclusion cysts + family h/o cancer + elevated CEA possibly suggesting GI malignancy; but “normal” scope 10yrs ago per pt </li></ul><ul><li>Premalignant : Paget’s Disease </li></ul>
    17. 17. So Now What?
    18. 18. “ Total Body CT Scan”
    19. 19. “ Total Body CT Scan”
    20. 20. CT Thorax
    21. 21. CT Abdomen
    22. 22. Homing in on the mediastinal mass… <ul><li>CT-guided FNA: </li></ul><ul><li>Moderately-differentiated neuroendocrine carcinoma: </li></ul>Small Cell Lung Cancer vs Medullary Thyroid Cancer
    23. 23. Tumor biopsy with Calcitonin stain
    24. 24. And the verdict is… <ul><li>Calcitonin stain confirms the final diagnosis: </li></ul><ul><li>Medullary Thyroid Cancer </li></ul>
    25. 25. Medullary Thyroid Cancer <ul><li>Neuroendocrine tumor of calcitonin-producing parafollicular C-cells </li></ul><ul><li>MTC C-cells also produce CEA </li></ul><ul><li>Accounts for ~5-10% of all primary thyroid cancer </li></ul>
    26. 26. Patterns of disease <ul><li>75% are sporadic </li></ul><ul><li>25% are autosomal dominant inherited forms: </li></ul><ul><li>a) MEN-2A </li></ul><ul><li>b) MEN-2B </li></ul><ul><li>c) Non-MEN Familial MTC </li></ul><ul><li>Prognosis: FMTC (best) > MEN-2A > Sporadic > MEN-2B (worst) </li></ul><ul><li>Vast majority of inherited forms, and some cases of sporadic disease, are associated with mutations in the RET proto-oncogene on chromosome 10 </li></ul>
    27. 27. Staging for MTC Stage I: T1, N0, M0 Stage II: T2-4, N0, M0 Stage III: Any T, N1, M0 Stage IV: Any T, any N, M1 Where T1 </= 1cm, T2 = 1-4cm, T3 > 4cm, T4 = direct invasion through capsule
    28. 28. Prognosis for our patient <ul><li>Saad et al (1984): median survival of 3-5 years in patients with stage III or IV disease </li></ul><ul><li>Dottorini et al (1996): 0% four-year survival rate in patients with stage IV disease </li></ul><ul><li>Hyer et al (2000): patients with stage IV comprise the worst prognostic group, but prolonged survival is still possible, with one patient surviving 16 yrs </li></ul>
    29. 29. Management of MTC <ul><li>Surgical management for localized disease and symptomatic relief in metastatic disease </li></ul><ul><li>Various chemotherapeutic regimens have failed to demonstrate response rates greater than 15-30% </li></ul><ul><li>Ongoing experimental trials with imatinib (Gleevec) at MD Anderson </li></ul><ul><li>XRT generally for palliation in metastatic disease </li></ul>
    30. 30. Clinical Course <ul><li>Repair of R femur with IM rod 1 week after admission </li></ul><ul><li>Poor surgical candidate for resection of primary tumor </li></ul><ul><li>Course of palliative XRT to pelvis 1 month later </li></ul><ul><li>Refused neck and mediastinal XRT </li></ul><ul><li>Discharged to nursing home </li></ul><ul><li>Recent readmission for R leg DVT, now on Coumadin </li></ul><ul><li>No current airway, esophageal, or great vessel symptoms </li></ul><ul><li>No s/s of pheochromocytoma or other MEN features </li></ul><ul><li>Current CEA = 467.9, Calcitonin = 824.0 (nl = 3-26) </li></ul>
    31. 31. Important learning points <ul><li>CEA : Not just colon cancer. </li></ul><ul><li>Tumor marker classically elevated in colon cancer, but also in malignancies of the breast, liver, and pancreas; may be produced by NE tumors such as MTC and small cell lung cancer </li></ul><ul><li>Used only as a marker of disease in patients with known history of CEA-producing tumor to monitor for recurrence or response to therapy </li></ul><ul><li>In the absence of known disease, it is neither sensitive nor specific and has no role in cancer screening </li></ul>
    32. 32. Important learning points <ul><li>Blastic and lytic lesions in bone metastases: What’s the significance? </li></ul><ul><li>While some tumors may produce mainly osteolytic lesions (eg kidney) and others mainly osteoblastic lesions (eg prostate), most metastatic disease produces both and may go through stages where one or the other predominates </li></ul>
    33. 33. Important Learning Points <ul><li>Thyroid cancer : with normal neck exam, normal TFTs, and pathologic fracture?! </li></ul><ul><li>While a nodule is the most common presenting feature, the absence of a palpable thyroid mass and/or cervical LAN does not rule out disease </li></ul><ul><li>Most are euthyroid, therefore normal TFTs do not rule out disease </li></ul><ul><li>All subtypes of thyroid cancer are well-known to metastasize to bone </li></ul>
    34. 34. Take-home message: <ul><li>Don’t forget the thyroid. </li></ul>
    35. 35. Resources <ul><li>Randolph GW and Maniar D. Medullary carcinoma of the thyroid. Cancer control 2000;7(3):253-61. </li></ul><ul><li>Hyer SL et al. Medullary thyroid cancer: multivariate analysis of prognostic factors influencing survival. Eur J Surg Oncol 2000;26:686-690. </li></ul><ul><li>Cheah WK et al. Complications of neck dissection for thyroid cancer. World J Surg 2002 Jun 6;26(8) </li></ul><ul><li>Moley JF, DeBenedetti MK. Patterns of nodal metastases in palpable medullary thyroid carcinoma: recommendations for extent of node dissection. Ann Surg 1999;229(6):880-8. </li></ul><ul><li>Kebebew E et al. Long-term results of reoperation and localizing studies in patients with persistent or recurrent medullary thyroid cancer. Arch Surg 2000;135:895-901. </li></ul><ul><li>Dotzenrath C et al. Is there any consensus in diagnostic and operative strategy with respect to medullary thyroid cancer? Langenbecks Arch Surg 2001 Feb;386(1):47-52. </li></ul><ul><li>Saad MF et al. Medullary carcinoma of the thyroid: a study of the clinical features of and prognostic factors in 161 patients. Medicine 1984;63:319-42. </li></ul>
    36. 36. Resources (cont.) <ul><li>Rougier P et el. The Values of Calcitonin and Carcinoembryonic Antigen in the Treatment and Management of Nonfamilial Medullary Thyroid Carcinoma. Cancer 1983;51(5):855-62. </li></ul><ul><li>Franz MG. Medullary Thyroid Cancer. Cancer Control 1997;4(1): 25-9. </li></ul><ul><li>Juweid M et al. Improved Detection of Medullary Thyroid Cancer with Radiolabeled Antibodies to Carcinoembryonic Antigen. J Clin Oncol 1996;14(4):1209-17. </li></ul><ul><li>Sherman SI. Clinical manifestations and staging of medullary thyroid carcinoma. UpToDate 2002. </li></ul><ul><li>Cotran et al. Robbins Pathologic Basis of Disease. 6 th ed. Philadelphia: Saunders, 1999. </li></ul><ul><li>Braunwald et al. Harrison’s Principles of Internal Medicine. 15 th ed. New York: McGraw-Hill, 2001. </li></ul><ul><li>Special thanks to Baylor SIMS and Meridale Vaught. </li></ul>
    37. 37. Limping toward a diagnosis: <ul><li>A work-up of non-traumatic hip pain </li></ul><ul><li>Presented by Travis Baggett </li></ul><ul><li>Baylor College of Medicine </li></ul><ul><li>Faculty mentor: Dr Ed Young </li></ul>QUESTIONS?

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