eMedicine Specialties > Otolaryngology and Facial Plastic Surgery > Pathology

Skin Cancer: Merkel Cell Carcinoma: Workup

Author: Michael J Pitman, MD, Assistant Professor, New York Medical College; Director, The Voice and Swallowing Institute; Director, Division of Laryngology, Department of Otolaryngology, New York Eye and Ear Infirmary
Coauthor(s): James M Pearson, MD, Staff Physician, Department of Otolaryngology - Head and Neck Surgery, New York Eye and Ear Infirmary; James D Williams, MD, FACS, Consulting Staff, Department of Ear, Nose and Throat, Granville Medical Center
Contributor Information and Disclosures

Updated: Nov 6, 2008

Workup

Laboratory Studies

Baseline laboratory studies should include a CBC count, a chemistry profile, and liver function tests.

Imaging Studies

  • No optimal imaging algorithm has been defined.
  • Because of the difficulties in distinguishing metastatic oat cell carcinoma from Merkel cell carcinoma (MCC), chest radiography should be performed.
  • Obtain CT scans of the chest, abdomen, and pelvis to rule out metastases.
  • Some have suggested that obtaining octreotide scanning may also be helpful for ruling out metastases. However, this study is not part of the standard evaluation.
  • The role of [18 F]2-fluoro-D-2-deoxyglucose (FDG) positron emission tomography (PET) remains undefined.
    • Recent reports indicate that FDG-PET may aid in the staging and following up Merkel cell carcinomas (MCCs).
    • Yao et al (2005) reported that pretreatment FDG-PET scans revealed metastatic disease in subcentimeter lymph nodes that were not appreciated on initial CT images.3 Likewise, posttreatment FDG-PET scans revealed responses to therapy, with the level of FDG uptake correlating with complete responses to treatment and with residual disease.

Histologic Findings

Diagnosing Merkel cell carcinoma (MCC) is difficult and requires a high degree of suspicion. Light microscopy, electron microscopy, and immunohistochemistry may be needed to confirm the diagnosis.

Light microscopy

On occasion, Merkel cell carcinomas (MCCs) may be diagnosed with histology alone, but confirmation with immunohistochemistry and/or electron microscopy is always encouraged. Diagnosis by means of light microscopy alone is difficult because the appearance of Merkel cell carcinomas (MCCs) is similar to that of many other undifferentiated small-cell neoplasms, especially other APUD tumors, such as metastatic oat cell carcinoma. In fact, 66% of Merkel cell carcinomas (MCCs) are misdiagnosed when studied with light microscopy alone.

These points emphasize the need to consider Merkel cell carcinoma (MCC) when small cell tumors are being diagnosed with light microscopy. Light microscopy reveals round-to-polygonal neoplastic cells that are compactly arranged. Rare fusiform cells are also observed. A ball-in-mitt arrangement of cells is often described, where 1 or 2 crescentic tumor cells wrap around a round tumor cell. A grenz zone usually separates the tumor from the epidermis. As a result, the epidermis is commonly spared because the Merkel cell carcinoma (MCC) alternatively extends into the subcutaneous tissues, vessels, and lymphatics.

Gould et al (1985) described a widely accepted histologic classification of Merkel cell carcinoma (MCC).4 The classification details 3 specific cellular patterns.

The most common pattern is the intermediate cell type; observed in over 50% of patients with Merkel cell carcinoma (MCC). These tumors display a large nest of cells without organoid architecture or recognizable palisading. A distinct disassociation exists between cells. Areas of focal necrosis and lymphocytic invasion are typical. Cytoplasm is moderate, nuclei are vesicular, and mitoses are abundant.

The trabecular cell type is observed in 25% of Merkel cell carcinomas (MCCs). It is believed to be the original tumor Toker described (1972).1 In this class, the cells are arranged in organoid clusters with interconnected trabeculae separated by strands of connective tissue. Clusters may show glandlike organization. Individual cells are compactly arranged round-to-polygonal cells. Cytoplasm is abundant, and the nuclei are round, centrally located, and vesicular. Pleomorphism and mitotic activity is mild to moderate.

The final and least common class is the small cell variation. This pattern consists of solid sheets and clusters of cells separated by abundant stroma, with large areas of necrosis. The cells are small with scant cytoplasm and hyperchromatic nuclei. Pleomorphism and mitoses are common.

Electron microscopy

Because of the difficulty in diagnosing Merkel cell carcinoma (MCC) with light microscopy, electron microscopy plays an important role in the diagnosis of Merkel cell carcinoma (MCC). The ultrastructure of the tumor is similar to that of the normal Merkel cell. The cells are round to ovoid and intimately apposed to adjacent tumor cells, with desmosomal junctions to surrounding keratinocytes. One of the most consistent findings is the aggregation of intermediate filaments in a paranuclear location. Other characteristic findings are membrane-bound, dense core granules. The granules are usually concentrated in the periphery or in dendritelike processes.

Immunohistochemistry

Immunohistochemistry is often used to confirm Merkel cell carcinoma (MCC). Merkel cell tumors stain positively for NSE, as would any APUD cell tumor. They also demonstrate perinuclear staining with antikeratin antibodies to low-molecular-weight cytokeratins 8, 18, and 19. These 2 markers are the most constant immunohistochemical markers and are often said to be present in 100% of Merkel cell carcinomas (MCCs). A third marker, neurofilament protein, is used to distinguish Merkel cell carcinoma (MCC) from oat cell carcinoma. Neurofilament protein is seen in nearly all Merkel cell carcinomas (MCCs) but few oat cell carcinomas.

Other markers present with variable frequency are chromogranin, synaptophysin, vasoactive intestinal peptide (VIP), calcitonin, bombesin, corticotropic hormone (ACTH), met-encephalon, gastrin, and somatostatin.

Finally, the absence of certain markers also helps in the diagnosis of Merkel cell carcinoma (MCC) by ruling out other tumors. S-100 is seen in melanoma, whereas leukocyte common antigen is present in lymphoma. Neither of these is found in Merkel cell carcinoma (MCC).

Staging

No universally accepted staging system for Merkel cell carcinoma (MCC) exists. Some have used the American Joint Committee on Cancer Staging System for skin cancer to stage Merkel cell carcinoma (MCC). Others use a staging system developed by the Memorial Sloan Kettering Cancer Center. This article uses the widely-used system suggested by Yiengpruksawan et al (1991), as follows:5

  • Stage I - Absence of lymphadenopathy
    • Stage IA - Tumors <2 cm
    • Stage IB - Tumors >2 cm
  • Stage II - Positive regional lymphadenopathy
  • Stage III - Evidence of distant metastases

At presentation, most patients have stage I disease (55%), followed by stage II (31%), and stage III (6%).

More on Skin Cancer: Merkel Cell Carcinoma

Overview: Skin Cancer: Merkel Cell Carcinoma
Workup: Skin Cancer: Merkel Cell Carcinoma
Treatment: Skin Cancer: Merkel Cell Carcinoma
Follow-up: Skin Cancer: Merkel Cell Carcinoma
Multimedia: Skin Cancer: Merkel Cell Carcinoma
References
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Further Reading

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Keywords

carcinoma, Merkel, Merkel cell carcinoma, Merkel cell carcinoma of the skin, MCC, trabecular carcinoma of the skin, neuroendocrine carcinoma of the skin, cutaneous neoplasm, ectodermal dysplasia, Bowen disease, squamous cell carcinoma, basal cell carcinoma, solar keratoses, lentigo maligna, B cell lymphoma, radiation exposure, keratoacanthoma, amelanotic melanoma, epidermal cysts, lymphoma, metastatic carcinoma of the skin, skin cancer, Merkel cell, skin tumor, metastatic oat cell carcinoma, lymphadenopathy, Mohs surgery, neck dissection, Merkel cell cancer

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Contributor Information and Disclosures

Author

Michael J Pitman, MD, Assistant Professor, New York Medical College; Director, The Voice and Swallowing Institute; Director, Division of Laryngology, Department of Otolaryngology, New York Eye and Ear Infirmary
Michael J Pitman, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Otolaryngology-Head and Neck Surgery, and Voice Foundation
Disclosure: Nothing to disclose.

Coauthor(s)

James M Pearson, MD, Staff Physician, Department of Otolaryngology - Head and Neck Surgery, New York Eye and Ear Infirmary
Disclosure: Nothing to disclose.

James D Williams, MD, FACS, Consulting Staff, Department of Ear, Nose and Throat, Granville Medical Center
James D Williams, MD, FACS is a member of the following medical societies: Alpha Omega Alpha, American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, American College of Surgeons, and Medical Society of the State of New York
Disclosure: Nothing to disclose.

Medical Editor

M Abraham Kuriakose, MD, DDS, FRCS, Chairman, Head and Neck Institute, Amrita Institute of Medical Sciences
M Abraham Kuriakose, MD, DDS, FRCS is a member of the following medical societies: American Association for Cancer Research, American Head and Neck Society, British Association of Oral and Maxillofacial Surgeons, and Royal College of Surgeons of England
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

M Sherif Said, MD, PhD, Assistant Professor of Pathology, Director of Head and Neck Pathology, Department of Pathology, University of Colorado Health Sciences Center
M Sherif Said, MD, PhD is a member of the following medical societies: American Medical Association, American Society for Clinical Pathologists, College of American Pathologists, and Southern Medical Association
Disclosure: Nothing to disclose.

CME Editor

Christopher L Slack, MD, Otolaryngology-Facial Plastic Surgery, Private Practice, Associated Coastal ENT; Medical Director, Treasure Coast Sleep Disorders
Christopher L Slack, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Arlen D Meyers, MD, MBA, Professor, Department of Otolaryngology-Head and Neck Surgery, University of Colorado School of Medicine
Arlen D Meyers, MD, MBA is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, and American Head and Neck Society
Disclosure: Covidien Corp Consulting fee Consulting; US Tobacco Corporation unstricted gift unknown

 
 
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