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


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