Dermatologic Manifestations of Merkel Cell Carcinoma Workup

  • Author: Christopher R Shea, MD; Chief Editor: Dirk M Elston, MD   more...
 
Updated: Nov 5, 2010
 

Imaging Studies

Radiography of the chest is indicated in Merkel cell carcinoma (MCC) to rule out the alternative diagnosis of cutaneous metastasis from a primary small cell neuroendocrine carcinoma (oat cell carcinoma) of the lung.

Staging CT or MRI studies are needed to assess the possibility of dissemination of primary Merkel cell carcinoma to the lymph nodes or the viscera.

Next

Procedures

Fine-needle aspiration may be helpful to assess recurrence or metastatic spread.

Previous
Next

Histologic Findings

Tumors cells are usually located intradermally; an intraepidermal component may also be present, and a purely intraepidermal (in situ) Merkel cell carcinoma rarely may be encountered. Reactive epidermal hyperplasia is frequent.

Several architectural patterns of intradermal tumor are recognized. The classic trabecular pattern consists of interconnecting strands of tumor cells in the dermis, with formation of cellular aggregates resembling glands or neural rosettes.[17] The intermediate pattern is the most common, and it exhibits large, solid nests of neoplastic cells. The least common, diffuse pattern consists of an infiltration of tumor cells among dermal collagen bundles, without the more distinctive organoid appearance of the trabecular pattern. A particular tumor often contains elements of all architectural patterns, with individual variation in the proportions represented.

Histologic appearance of nodular Merkel cell carciHistologic appearance of nodular Merkel cell carcinoma. Dermal nodule with a cohesive, expansile growth of basophilic cells. High-power view demonstrates an open chromatin patHigh-power view demonstrates an open chromatin pattern and a high mitotic index.

The tumor is usually composed of round, small, dark cells with conspicuous nucleoli and open chromatin with peripheral heterochromatin (salt-and-pepper pattern). Less commonly, Merkel cell carcinoma cells may simulate lymphoma, or may exhibit plasmacytoid, clear cell, anaplastic, or spindle-cell features. Mitotic figures and apoptotic bodies are often numerous. Vascular or lymphatic invasion is not uncommon. Histologic variants of Merkel cell carcinoma include the desmoplastic, epidermotropic (resembling mycosis fungoides), and pagetoid (resembling Paget disease[18] or melanoma) types, and tumors with focal true glandular or squamous differentiation.[19, 20, 21] Merkel cell carcinoma has been associated with squamous cell carcinoma, basal cell carcinoma, adnexal tumors, and trichilemmal cyst.

Merkel cell carcinoma with a focus of squamous difMerkel cell carcinoma with a focus of squamous differentiation. Prominent in situ nested component of Merkel cell Prominent in situ nested component of Merkel cell carcinoma, simulating malignant melanoma.

Immunohistochemistry is very helpful. Cytokeratin 20 is expressed in a dotlike paranuclear or crescentic pattern; other low molecular weight (MW) cytokeratin antibodies (eg, CAM5.2, MNF116), while less specific, react in a similar localization pattern. Neurofilament is also expressed in the cytoplasm of most Merkel cell carcinoma. The above findings support the diagnosis of primary Merkel cell carcinoma of the skin and tend to rule out metastatic neuroendocrine carcinoma, as from a pulmonary primary. The CK20 expression is so sensitive and specific that it has largely replaced traditional markers of neuroendocrine differentiation (ie, synaptophysin, chromogranin) as the initial antibody panel of choice; however, the latter may be helpful adjuncts in difficult cases.[22]

Dotlike paranuclear pattern of cytokeratin immunolDotlike paranuclear pattern of cytokeratin immunolocalization.

Electron microscopic findings are characteristic, revealing a lobulated nucleus that may contain rodlets. The cytoplasm is electron-lucent and contains a prominent Golgi apparatus and numerous ribosomes. Intermediate filaments are numerous and often assume a parallel or whorled arrangement near the nucleus, accounting for the dotlike pattern of cytokeratin distribution visualized by immunohistochemistry.[23] Desmosomes may be present. Most diagnostic is the dense core granule (80-120 nm in diameter), the source, and the locus of the neuroendocrine peptides.

Electron micrograph of Merkel cell carcinoma showiElectron micrograph of Merkel cell carcinoma showing a dense core granule (arrow). Electron micrograph of Merkel cell carcinoma showiElectron micrograph of Merkel cell carcinoma showing whorled bundles of intermediate filaments (arrow) near nucleus in Merkel cell carcinoma.

Cytologic preparations from fine-needle aspirates (FNAs) demonstrate a loosely cohesive pattern of small to intermediate-sized cells with round nuclei, finely granular chromatin, a thin rim of cytoplasm, and (infrequently) pseudorosette formation. Immunocytochemistry may be helpful.[24]

Pseudorosette formation in Merkel cell carcinoma. Pseudorosette formation in Merkel cell carcinoma.
Previous
Next

Staging

According to the American Joint Committee on Cancer guidelines, carcinoma of the skin is staged by the status of T (primary tumor), N (lymph node), and M (metastasis). The definitions are as follows:

Table 1. Tumor Status (Open Table in a new window)

TXPrimary tumor cannot be assessed
T0No evidence of primary tumor
TisCarcinoma in situ
T1Tumor 2 cm or less in greatest dimension
T2Tumor >2 cm but not >5 cm in greatest dimension
T3Tumor >5 cm in greatest dimension
T4Tumor invades deep extradermal structures (ie, cartilage, skeletal muscle, bone)

Note: In the case of multiple simultaneous tumors, the tumor with the highest T category is classified and the number of separate tumors is indicated in parentheses, such as T2 (5).

Table 2. Node and Metastasis Status (Open Table in a new window)

NXRegional lymph nodes cannot be assessed
N0No regional lymph node metastasis
N1Regional lymph metastasis
MXDistant metastasis cannot be assessed
M0No distant metastasis
M1Distant metastasis

Table 3. Stage Grouping (Open Table in a new window)

Stage 0TisN0M0
Stage IT1N0M0
Stage IIT2N0M0
(or)T3N0M0
Stage IIIT4N0M0
(or)Any TN1M0
Stage IVAny TAny NM1

Sentinel lymph nodes may be examined by breadloafing and subsequent analysis of keratin expression with an antikeratin cocktail. Because dendritic cells in the lymph nodes may express keratin, in case of doubt anti-CK20 antibodies may be useful to rule out metastatic Merkel cell carcinoma. A recent analysis on a large number of patients indicates that, as in other solid tumors, positive sentinel lymph nodes correlate with impaired prognosis.[25]

Previous
Proceed to Treatment & Management
 
 
Contributor Information and Disclosures
Author

Christopher R Shea, MD  Professor and Chief, Section of Dermatology, Department of Medicine, University of Chicago

Christopher R Shea, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Society of Dermatopathology, Arthur Purdy Stout Society, Association of Professors of Dermatology, Chicago Dermatological Society, Dermatology Foundation, Illinois Dermatological Society, International Society of Dermatopathology, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Coauthor(s)

Victor G Prieto, MD, PhD  Director of Dermatopathology, Professor, Departments of Pathology and Dermatology, University of Texas MD Anderson Cancer Center

Victor G Prieto, MD, PhD is a member of the following medical societies: American Association for the Advancement of Science, American Medical Association, American Society for Clinical Pathology, American Society of Dermatopathology, College of American Pathologists, European Society of Pathology, International Society of Dermatopathology, Society for Investigative Dermatology, and United States and Canadian Academy of Pathology

Disclosure: Nothing to disclose.

Specialty Editor Board

Susan M Swetter, MD  Director, Pigmented Lesion and Melanoma Program, Professor, Department of Dermatology, Stanford University Medical Center, Veterans Affairs Palo Alto Health Care System

Susan M Swetter, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, American Society of Clinical Oncology, Eastern Cooperative Oncology Group, Pacific Dermatologic Association, Society for Investigative Dermatology, Society for Melanoma Research, and Women's Dermatologic Society

Disclosure: Nothing to disclose.

Richard P Vinson, MD  Assistant Clinical Professor, Department of Dermatology, Texas Tech University School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association

Disclosure: Nothing to disclose.

John G Albertini, MD  Consulting Staff, Dermatologic Surgery, The Skin Surgery Center; Program Director, ACGME accredited Fellowship in Procedural Dermatology

John G Albertini, MD is a member of the following medical societies: American Academy of Dermatology and American College of Mohs Micrographic Surgery and Cutaneous Oncology

Disclosure: Nothing to disclose.

Joel M Gelfand, MD, MSCE  Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania

Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology

Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds Investigator; Genentech Grant/research funds investigator; Centocor Consulting fee Consulting; Abbott Grant/research funds investigator; Abbott Consulting fee Consulting; Novartis investigator; Pfizer Grant/research funds investigator; Celgene Consulting fee DMC Chair; NIAMS and NHLBI Grant/research funds investigator

Chief Editor

Dirk M Elston, MD  Director, Department of Dermatology, Geisinger Medical Center

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

References

  1. Nakafusa J, Narisawa Y, Shinogi T, et al. Changes in the number of Merkel cells with the hair cycle in hair discs on rat back skin. Br J Dermatol. Nov 2006;155(5):883-9. [Medline].

  2. Leonard JH, Hayard N. Loss of heterozygosity of chromosome 13 in Merkel cell carcinoma. Genes Chromosomes Cancer. Sep 1997;20(1):93-7. [Medline].

  3. Leonard JH, Williams G, Walters MK, Nancarrow DJ, Rabbitts PH. Deletion mapping of the short arm of chromosome 3 in Merkel cell carcinoma. Genes Chromosomes Cancer. Feb 1996;15(2):102-7. [Medline].

  4. Van Gele M, Speleman F, Vandesompele J, Van Roy N, Leonard JH. Characteristic pattern of chromosomal gains and losses in Merkel cell carcinoma detected by comparative genomic hybridization. Cancer Res. Apr 1 1998;58(7):1503-8. [Medline].

  5. Van Gele M, Van Roy N, Ronan SG, et al. Molecular analysis of 1p36 breakpoints in two Merkel cell carcinomas. Genes Chromosomes Cancer. Sep 1998;23(1):67-71. [Medline].

  6. Vortmeyer AO, Merino MJ, Böni R, Liotta LA, Cavazzana A, Zhuang Z. Genetic changes associated with primary Merkel cell carcinoma. Am J Clin Pathol. May 1998;109(5):565-70. [Medline].

  7. Hodgson NC. Merkel cell carcinoma: changing incidence trends. J Surg Oncol. Jan 1 2005;89(1):1-4. [Medline].

  8. Pitale M, Sessions RB, Husain S. An analysis of prognostic factors in cutaneous neuroendocrine carcinoma. Laryngoscope. Mar 1992;102(3):244-9. [Medline].

  9. Mott RT, Smoller BR, Morgan MB. Merkel cell carcinoma: a clinicopathologic study with prognostic implications. J Cutan Pathol. Mar 2004;31(3):217-23. [Medline].

  10. Gipponi M. Clinical applications of sentinel lymph-node biopsy for the staging and treatment of solid neoplasms. Minerva Chir. Aug 2005;60(4):217-33. [Medline].

  11. Gupta SG, Wang LC, Penas PF, Gellenthin M, Lee SJ, Nghiem P. Sentinel lymph node biopsy for evaluation and treatment of patients with Merkel cell carcinoma: The Dana-Farber experience and meta-analysis of the literature. Arch Dermatol. Jun 2006;142(6):685-90. [Medline].

  12. Schmalbach CE, Lowe L, Teknos TN, Johnson TM, Bradford CR. Reliability of sentinel lymph node biopsy for regional staging of head and neck Merkel cell carcinoma. Arch Otolaryngol Head Neck Surg. Jul 2005;131(7):610-4. [Medline].

  13. Wasserberg N, Schachter J, Fenig E, Feinmesser M, Gutman H. Applicability of the sentinel node technique to Merkel cell carcinoma. Dermatol Surg. Feb 2000;26(2):138-41. [Medline].

  14. Gooptu C, Woollons A, Ross J, et al. Merkel cell carcinoma arising after therapeutic immunosuppression. Br J Dermatol. Oct 1997;137(4):637-41. [Medline].

  15. Shaw M, Warren S, Groben P, Gulley ML. No evidence of Epstein-Barr virus association with Merkel cell carcinoma. J Cutan Pathol. Sep 2006;33(9):624-8. [Medline].

  16. Feng H, Shuda M, Chang Y, Moore PS. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science. Feb 22 2008;319(5866):1096-100. [Medline].

  17. Toker C. Trabecular carcinoma of the skin. Arch Dermatol. Jan 1972;105(1):107-10. [Medline].

  18. Hashimoto K, Lee MW, D'Annunzio DR, Balle MR, Narisawa Y. Pagetoid Merkel cell carcinoma: epidermal origin of the tumor. J Cutan Pathol. Nov 1998;25(10):572-9. [Medline].

  19. Gould E, Albores-Saavedra J, Dubner B, Smith W, Payne CM. Eccrine and squamous differentiation in Merkel cell carcinoma. An immunohistochemical study. Am J Surg Pathol. Oct 1988;12(10):768-72. [Medline].

  20. Iacocca MV, Abernethy JL, Stefanato CM, Allan AE, Bhawan J. Mixed Merkel cell carcinoma and squamous cell carcinoma of the skin. J Am Acad Dermatol. Nov 1998;39(5 Pt 2):882-7. [Medline].

  21. Miller RW, Rabkin CS. Merkel cell carcinoma and melanoma: etiological similarities and differences. Cancer Epidemiol Biomarkers Prev. Feb 1999;8(2):153-8. [Medline].

  22. Miettinen M. Keratin 20: immunohistochemical marker for gastrointestinal, urothelial, and Merkel cell carcinomas. Mod Pathol. May 1995;8(4):384-8. [Medline].

  23. Shah IA, Netto D, Schlageter MO, Muth C, Fox I, Manne RK. Neurofilament immunoreactivity in Merkel-cell tumors: a differentiating feature from small-cell carcinoma. Mod Pathol. Jan 1993;6(1):3-9. [Medline].

  24. Collins BT, Elmberger PG, Tani EM, Bjornhagen V, Ramos RR. Fine-needle aspiration of Merkel cell carcinoma of the skin with cytomorphology and immunocytochemical correlation. Diagn Cytopathol. Apr 1998;18(4):251-7. [Medline].

  25. Lemos BD, Storer BE, Iyer JG, Phillips JL, Bichakjian CK, Fang LC, et al. Pathologic nodal evaluation improves prognostic accuracy in Merkel cell carcinoma: analysis of 5823 cases as the basis of the first consensus staging system. J Am Acad Dermatol. Nov 2010;63(5):751-61. [Medline]. [Full Text].

  26. Voog E, Biron P, Martin JP, Blay JY. Chemotherapy for patients with locally advanced or metastatic Merkel cell carcinoma. Cancer. Jun 15 1999;85(12):2589-95. [Medline].

  27. Decker RH, Wilson LD. Role of radiotherapy in the management of merkel cell carcinoma of the skin. J Natl Compr Canc Netw. Aug 2006;4(7):713-8. [Medline].

  28. Meeuwissen JA, Bourne RG, Kearsley JH. The importance of postoperative radiation therapy in the treatment of Merkel cell carcinoma. Int J Radiat Oncol Biol Phys. Jan 15 1995;31(2):325-31. [Medline].

  29. Senchenkov A, Barnes SA, Moran SL. Predictors of survival and recurrence in the surgical treatment of merkel cell carcinoma of the extremities. J Surg Oncol. Mar 1 2007;95(3):229-34. [Medline].

  30. Veness MJ, Perera L, McCourt J, et al. Merkel cell carcinoma: improved outcome with adjuvant radiotherapy. ANZ J Surg. May 2005;75(5):275-81. [Medline].

  31. O'Connor WJ, Roenigk RK, Brodland DG. Merkel cell carcinoma. Comparison of Mohs micrographic surgery and wide excision in eighty-six patients. Dermatol Surg. Oct 1997;23(10):929-33. [Medline].

  32. Leong SP. Selective sentinel lymphadenectomy for malignant melanoma, Merkel cell carcinoma, and squamous cell carcinoma. Cancer Treat Res. 2005;127:39-76. [Medline].

  33. Kokoska ER, Kokoska MS, Collins BT, Stapleton DR, Wade TP. Early aggressive treatment for Merkel cell carcinoma improves outcome. Am J Surg. Dec 1997;174(6):688-93. [Medline].

  34. Takenaka H, Kishimoto S, Shibagaki R, Nagata M, Yasuno H. Merkel cell carcinoma with partial spontaneous regression: an immunohistochemical, ultrastructural, and TUNEL labeling study. Am J Dermatopathol. Dec 1997;19(6):614-8. [Medline].

  35. Ng L, Beer TW, Murray K. Vascular density has prognostic value in Merkel cell carcinoma. Am J Dermatopathol. Oct 2008;30(5):442-5. [Medline].

  36. Amo-Takyi BK, Tietze L, Tory K, et al. Diagnostic relevance of chromosomal in-situ hybridization in Merkel cell carcinoma: targeted interphase cytogenetic tumour analyses. Histopathology. Feb 1999;34(2):163-9. [Medline].

  37. Haag ML, Glass LF, Fenske NA. Merkel cell carcinoma. Diagnosis and treatment. Dermatol Surg. Aug 1995;21(8):669-83. [Medline].

  38. Miettinen M, Lasota J. Cutaneous lymphoma-simulating Merkel cell carcinoma-molecular genetic demonstration of a clonal disease with divergent immunophenotypes. Mod Pathol. Sep 1995;8(7):769-74. [Medline].

  39. Moll I, Moll R. Early development of human Merkel cells. Exp Dermatol. Nov 1992;1(4):180-4. [Medline].

  40. Pilotti S, Rilke F, Bartoli C, Grisotti A. Clinicopathologic correlations of cutaneous neuroendocrine Merkel cell carcinoma. J Clin Oncol. Dec 1988;6(12):1863-73. [Medline].

  41. Plaza JA, Suster S. The Toker tumor: spectrum of morphologic features in primary neuroendocrine carcinomas of the skin (Merkel cell carcinoma). Ann Diagn Pathol. Dec 2006;10(6):376-85. [Medline].

  42. Ratner D, Nelson BR, Brown MD, Johnson TM. Merkel cell carcinoma. J Am Acad Dermatol. Aug 1993;29(2 Pt 1):143-56. [Medline].

  43. Savage P, Constenla D, Fisher C, Thomas JM, Gore ME. The natural history and management of Merkel cell carcinoma of the skin: a review of 22 patients treated at the Royal Marsden Hospital. Clin Oncol (R Coll Radiol). 1997;9(3):164-7. [Medline].

  44. Skelton HG, Smith KJ, Hitchcock CL, McCarthy WF, Lupton GP, Graham JH. Merkel cell carcinoma: analysis of clinical, histologic, and immunohistologic features of 132 cases with relation to survival. J Am Acad Dermatol. Nov 1997;37(5 Pt 1):734-9. [Medline].

  45. Smith DE, Bielamowicz S, Kagan AR, Anderson PJ, Peddada AV. Cutaneous neuroendocrine (Merkel cell) carcinoma. A report of 35 cases. Am J Clin Oncol. Jun 1995;18(3):199-203. [Medline].

  46. Suárez C, Rodrigo JP, Ferlito A, Devaney KO, Rinaldo A. Merkel cell carcinoma of the head and neck. Oral Oncol. Sep 2004;40(8):773-9. [Medline].

  47. Tai PT, Yu E, Winquist E, et al. Chemotherapy in neuroendocrine/Merkel cell carcinoma of the skin: case series and review of 204 cases. J Clin Oncol. Jun 2000;18(12):2493-9. [Medline].

 
Previous
Next
 
Large, violaceous nodule of Merkel cell carcinoma on the antecubital fossa. Courtesy of Dr. Jonathan Cook.
Histologic appearance of nodular Merkel cell carcinoma. Dermal nodule with a cohesive, expansile growth of basophilic cells.
High-power view demonstrates an open chromatin pattern and a high mitotic index.
Pseudorosette formation in Merkel cell carcinoma.
Merkel cell carcinoma with a focus of squamous differentiation.
Prominent in situ nested component of Merkel cell carcinoma, simulating malignant melanoma.
Electron micrograph of Merkel cell carcinoma showing a dense core granule (arrow).
Electron micrograph of Merkel cell carcinoma showing whorled bundles of intermediate filaments (arrow) near nucleus in Merkel cell carcinoma.
Dotlike paranuclear pattern of cytokeratin immunolocalization.
Table 1. Tumor Status
TXPrimary tumor cannot be assessed
T0No evidence of primary tumor
TisCarcinoma in situ
T1Tumor 2 cm or less in greatest dimension
T2Tumor >2 cm but not >5 cm in greatest dimension
T3Tumor >5 cm in greatest dimension
T4Tumor invades deep extradermal structures (ie, cartilage, skeletal muscle, bone)
Table 2. Node and Metastasis Status
NXRegional lymph nodes cannot be assessed
N0No regional lymph node metastasis
N1Regional lymph metastasis
MXDistant metastasis cannot be assessed
M0No distant metastasis
M1Distant metastasis
Table 3. Stage Grouping
Stage 0TisN0M0
Stage IT1N0M0
Stage IIT2N0M0
(or)T3N0M0
Stage IIIT4N0M0
(or)Any TN1M0
Stage IVAny TAny NM1
Previous
Next
 
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.