Hematology/ Oncology Grand RoundsÂ

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<ul><li> 1. Hematology/Oncology Grand Rounds September 3, 2004 Merkel Cell Carcinoma Presented by Coy Heldermon </li> <li> 2. <ul><li>CC: Bleeding bottom </li></ul><ul><li>HPI: 57yo WM fell in his backyard while getting off of a ladder and bruised his R buttock. Hematoma formed and over several days the skin broke down and he noticed bleeding. He presented to his PCP who cauterized the bleeding sites and took biopsies. </li></ul><ul><li>PMH: prostatectomy </li></ul><ul><li>tonsillectomy/adenoidectomy </li></ul><ul><li>mononucleosis as teen </li></ul><ul><li>FH: Aunt Br Ca, Uncle Lung Ca </li></ul><ul><li>SH: Married, 3 grown children, remote 14pyh of cigarettes, social ETOH use. </li></ul><ul><li>ROS: Negative except pain and bleeding at R buttock </li></ul><ul><li>PE: remarkable only for necrosis at 2cm hematoma site on mid R buttock </li></ul></li> <li> 3. <ul><li>Clinical Course </li></ul><ul><li>June 02 pathology read as small cell neoplasm at an OSH and referred to BJH with final reading of Merkel cell carcinoma. Pt underwent local excision at R buttock with iliac lymph node dissection and spermatic cord excision. </li></ul><ul><li>Surgical margins were positive and 3/3 lymph nodes had disease. </li></ul><ul><li>CT chest, abdomen, pelvis demonstrated no evidence of metastatic disease. </li></ul><ul><li>October 02 Pt. referred to BJH Oncology. Pt received 3 cycles vincristine/adriamycin/cytoxan followed by radiation therapy and concurrent cisplatin/etoposide. </li></ul><ul><li>September 03 CT/PET reveals metastatic disease in the lungs, pancreas, L femoral neck, scapula, iliac and sacral lymph node chains, chest wall and a bone lesion at S4. </li></ul><ul><li>Pt underwent 5 cycles of cisplatin/irinotecan. </li></ul><ul><li>May 04 CT - Resolution of chest wall lesion and decreased size of remaining lesions. </li></ul><ul><li>The patients therapy was only complicated by the expected periodic nausea and cytopenias with persistent anemia. </li></ul></li> <li> 4. Merkel Cell <ul><li>So what is a Merkel cell? </li></ul><ul><li>identified in 1875 by Friedrich Sigmund Merkel, President of University of Rostock, professor of anatomy &amp; physician. Dr. Merkel identified the cell as a component of the touch receptor </li></ul>Arch Mikrosc Anat 11:636-652, 1875 </li> <li> 5. Merkel Cell <ul><li>Nondendritic, nonkeratinocytic epidermal cell near the basal layer, usually directly associated with nerve terminals especially near hair follicles and sweat gland ridges. </li></ul><ul><li>Some may be in the dermis but not associated with nerve cells. </li></ul>Figure of Sinus Hair Follicle: G-sebaceous gland, B- hair bulb, T- nerve terminus, M- merkel cell Anat Rec. Mar;271A(1):225-39, 2003 </li> <li> 6. Merkel Cell <ul><li>Slow adapting type I mechanoreceptor </li></ul><ul><li>Contain dense core granules similar to neurosecretory granules. </li></ul><ul><li>Thought to release glutamate (among other things) in response to mechanical stimulation. </li></ul><ul><li>Likely of neural crest origin. </li></ul><ul><li>Possibly not the cell of origin of Merkel cell carcinoma. </li></ul>Figure of Merkel cell (M) nerve ending (T) demonstrating dense core granules. Anat Rec. Mar;271A(1):225-39, 2003 </li> <li> 7. Merkel Cell Carcinoma <ul><li>1 st described by Toker in 1972 as a trabecular cancer of the dermis with high lymphatic metastatic risk and found mainly in elderly patients. (Arch Dermatol 1972;105:107-110) </li></ul><ul><li>U.S. Annual Incidence is ~0.4/100,000 </li></ul><ul><li>U.S. Median age is ~70 years </li></ul><ul><li>90% are found in caucasians, ~80% are in men. </li></ul><ul><li>80% are liver&gt; lung&gt; bones&gt; brain </li></ul>J Clin Onc 20(2): 588-598, 2002 Int J Derm 42:669-676, 2003 </li> <li> 9. Merkel Cell Carcinoma <ul><li>Work-up: </li></ul><ul><li>CT to assess regional lymph node involvement. </li></ul><ul><li>CXR to evaluate for lung metastases. </li></ul><ul><li>Sentinel node biopsy to evaluate lymphatic extension and thus efficacy of local therapy. </li></ul></li> <li> 10. Merkel Cell Carcinoma Pathology <ul><li>Pathology is of three types often in combination. </li></ul><ul><li>Solid (50%) irregular nests of intermediate sized basophilic cells in dense fibrous connective tissue. </li></ul><ul><li>Diffuse (42%)- small irregular hyperchromatic cells in diffusely infiltrating sheets. </li></ul><ul><li>Trabecular (8%)- irregular cords or ribbons of basophilic cells. </li></ul>s d t J Clin Onc 20(2): 588-598, 2002 </li> <li> 11. Merkel Cell Carcinoma <ul><li>Tumor often is necrotic and preferentially invades vascular and perineural spaces. </li></ul><ul><li>Invasion beyond the dermis is a predictor of metastases - 78% metastatic vs 29% metastatic in those with tumor confined to dermis. </li></ul></li> <li> 12. Merkel Cell Carcinoma <ul><li>Cells typically have prominent ovoid nuclei, dispersed chromatin, sparse cytoplasm, conspicuous nucleoli, and multiple neurosecretory granules </li></ul>Int J Derm 42:669-676, 2003 </li> <li> 13. Merkel Cell Carcinoma <ul><li>Histochemistry is positive for CK8, CK 18, CK20, somatostatin receptor, chromogranin A(from neuroendocrine granules), neuron specific enolase, &amp; synaptophysin(from the pre-synaptic vesicles) </li></ul><ul><li>CK7 and TTF-1(thyroid transcription factor) are negative, distinguishing MCC from SCLC </li></ul></li> <li> 14. Merkel Cell Carcinoma CK 18 Stain CK20 Stain Int J Derm 42:669-676, 2003 J Clin Onc 20(2): 588-598, 2002 </li> <li> 15. Merkel Cell Carcinoma Staging <ul><li>Two staging systems are commonly used, The AJCC system and the Yiengpruksawan system (used more often) </li></ul><ul><li>Ys system is </li></ul><ul><li>Stage I for no nodal dz </li></ul><ul><li>Stage II for nodal disease </li></ul><ul><li>Stage III for systemic metastases </li></ul>AJCC for Skin Cancers </li> <li> 16. Merkel Cell Carcinoma Treatment J Clin Onc 20(2): 588-598, 2002 </li> <li> 17. Merkel Cell Carcinoma Treatment Options Int J Derm 42:669-676, 2003 </li> <li> 18. Merkel Cell Carcinoma Treatment Options <ul><li>Other regimens in the literature include: </li></ul><ul><li>cyclophosphamide, doxorubicin, vincristine </li></ul><ul><li>cyclophosphamide, epirubicin, vincristine </li></ul><ul><li>cyclophosphamide, doxorubicin, vincristine + prednisone </li></ul><ul><li>cyclophosphamide, doxorubicin, vincristine alternating with cisplatin &amp; etoposide </li></ul><ul><li>doxorubicin, ifosfamide </li></ul><ul><li>cisplatin +/- doxorubicin </li></ul><ul><li>doxorubicin </li></ul><ul><li>mitoxantrone </li></ul><ul><li>Cyclophosphamide, anthracyclines and cisplatin are the most commonly used drugs in the literature. </li></ul><ul><li>Response rates for multidrug regimens are reported at 60-70%. </li></ul></li> <li> 19. Merkel Cell Carcinoma Survival J Clin Onc 20(2): 588-598, 2002 </li> <li> 20. Merkel Cell Carcinoma Future Directions <ul><li>TNF-alpha </li></ul><ul><li>interferon-alpha-2a/b </li></ul><ul><li>Bcl-2 antisense </li></ul></li> <li> 21. Bibliography <ul><li>Halata Z, Grim M, Bauman KI. Friedrich Sigmund Merkel and his "Merkel cell", morphology, development, and physiology: review and new results. Anat Rec. 2003 Mar;271A(1):225-39 </li></ul><ul><li>Agelli M, Clegg LX. Epidemiology of primary Merkel cell carcinoma in the United States.J Am Acad Dermatol 2003; 49:832-841 </li></ul><ul><li>Mendenhall WM, Mendenhall CM, Mendenhall NP. Merkel Cell Carcinoma. Laryngoscope 2004; 114:906-910 </li></ul><ul><li>Yiengpruksawan A, Coit DG, Thaler HT, et al. Merkel cell carcinoma. Prognosis and management. Arch Surg 1991; 126:1514-1519 </li></ul><ul><li>Mott RT, Smoller BR, Morgan MB. Merkel cell carcinoma: a clinicopathologic study with prognostic implications. J Cutan Pathol 2004; 31:217-223 </li></ul><ul><li>Krasagakis K, Tosca AD. Overview of Merkel cell carcinoma and recent advances in research. Int J Derm 2003; 42:669-676 </li></ul><ul><li>Goessling W, McKee PH, Mayer RJ. Merkel cell carcinoma. J Clin Onc 2002; 20:588-598 </li></ul><ul><li>George TK, di Santagnese PA, Bennett JM. Chemotherapy for metastatic Merkel cell carcinoma. Cancer 1985; 56:1034-1038 </li></ul><ul><li>Tai PTH, Yu E, Winquist E, Hammond A, Stitt L, Tonita J, Gilchrist J. Chemotherapy in Neuroendocrine/Merkel cell carcinoma of the skin: case series and review of 204 cases. J Clin Onc 2000; 18:2493-2499 </li></ul></li> </ul>