Testing & Diagnosis / Disease stages

Disease stages

The stage at diagnosis is by far the single most important measure of the chance that the cancer will return.

Overview of Merkel cell carcinoma stages

In 2010, the American Joint Committee on Cancer first adopted a specific system to use for staging MCC. Since 2010 the 7th edition MCC staging system was in use to stage stage Physicians determine the stage of cancer by performing physical exams and tests. Stages describe the extent of cancer within the body, especially whether the disease has spread (metastasized) from the primary site to other parts of the body. Merkel cell carcinoma Merkel cell carcinoma A skin cancer composed of cells that look microscopically similar to normal Merkel cells present in the skin. MCC was first described in 1972 and only in the 1990s was the CK20 antibody developed to make it easily identifiable by pathologists. Many doctors and patients are not aware of this cancer because of its recent description and relative rarity (~2,000 cases/year in the US--roughly 30 times less common than melanoma). About 40% of patients treated for MCC will experience a recurrence, making it far more aggressive than most other types of skin cancer, including melanoma. . This system is the first international “consensus” staging system and it replaced five conflicting systems that were all in use simultaneously. The system was based on an analysis of over 5000 patients using the National Cancer Cancer A term used to describe diseases in which abnormal cells continually divide without normal regulation. Cancerous cells may invade surrounding tissues and may spread to other regions of the body via blood and the lymphatic system. Database as well as an extensive review of the literature. As of 2018, MCC Staging is carried out using the 8th Edition of the AJCC Staging Manual.

Stages I & II MCC are defined as disease that is localized to the skin at the primary site primary site The area of the body where the abnormal tissue first appeared. . Stage I is for primary lesions less than or equal to 2 centimeters, and stage II is for primary lesions greater than 2 cm. Stage III is defined as disease that involves nearby lymph nodes (regional lymph nodes). Stage IV disease is found beyond regional lymph nodes.

A Closer Look

This staging system, published in the AJCC 8th Edition Manual, takes into account whether an MCC patient’s lymph nodes were tested for spread of the cancer simply by physical exam (clinical staging) or via microscopic/pathologic testing such as by sentinel lymph node biopsy. Although having a node biopsy requires surgery, it results in a much more accurate prediction of whether the cancer will spread or not, and should be considered in most cases.

Determining the stage of Merkel cell carcinoma

MCC is divided into stages depending on the size of the primary tumor and extent of disease in the lymph nodes and elsewhere in the body (metastasis). The stage at diagnosis is the major determinant of the chance for later spread (metastasis) and treatment options.

8th Edition MCC Staging Sytem Table

Stage Primary Tumor Lymph Node Metastasis
 0  In situ (within epidermis only) No regional lymph node metastasis No distant metastasis
 I Clinical* ≤ 2 cm maximum tumor dimension Nodes negative by clinical exam
(no pathological exam performed)
No distant metastasis
 I Pathological**  ≤ 2 cm maximum tumor dimension Nodes negative by pathologic exam No distant metastasis
 IIA Clinical > 2 cm tumor dimension Nodes negative by clinical exam
(no pathological exam performed)
No distant metastasis
 IIA Pathological > 2 cm tumor dimension Nodes negative by pathological exam No distant metastasis
 IIB Clinical Primary tumor invades bone, muscle, fascia, or cartilage Nodes negative by clinical exam
(no pathological exam performed)
No distant metastasis
 IIB Pathological Primary tumor invades bone, muscle, fascia, or cartilage Nodes negative by pathologic exam No distant metastasis
 III Clinical Any size / depth tumor Nodes positive by clinical exam
(no pathological exam performed)
No distant metastasis
 IIIA Pathological Any size / depth tumor Nodes positive by pathological exam only
(nodal disease not apparent on clinical exam)
No distant metastasis
Not detected (“unknown primary”) Nodes positive by clinical exam, and confirmed via pathological exam No distant metastasis
 IIIB Pathological  Any size / depth tumor Nodes positive by clinical exam, and confirmed via pathological exam OR in-transit metastasis***  No distant metastasis
 IV Clinical   Any +/- regional nodal involvement Distant metastasis
detected via clinical exam
 IV Pathological   Any +/- regional nodal involvement Distant metastasis
confirmed via pathological exam


* Clinical detection of nodal or metastatic metastatic Having to do with the spread of cancer from a primary site of origin to distant areas beyond the draining lymph nodes. disease may be via inspection, palpation, and/or imaging

**Pathological detection/confirmation of nodal disease may be via sentinel lymph node biopsy sentinel lymph node biopsy Removal and examination of the "sentinel" lymph node(s). Sentinel nodes are the first lymph nodes to which cancer cells spread from a primary lesion. To identify the sentinel lymph node(s), a radioactive substance and/or dye is injected near the primary lesion. The surgeon uses a Geiger counter to find the lymph node(s) containing the radioactive substance or looks for the lymph node(s) stained by the dye. The surgeon then removes the sentinel lymph node(s) and sends them to a pathologist to check for the presence of cancer. , lymphadenectomy, or fine needle biopsy biopsy The removal of cells or tissue in order to determine the presence, characteristics, or extent of a disease by a pathologist usually using microscopic analysis. ; and pathological confirmation of metastatic disease may be via biopsy of the suspected metastasis
***In transit metastasis: a tumor distinct from the primary lesion primary lesion The abnormal tissue that appeared first. The majority of Merkel cell carcinoma primary lesions occur in sun-exposed areas. In some cases of MCC (approximately 11%) the patient has no primary lesion and instead has a nodal presentation (disease in a lymph node only). In these cases the primary lesion likely was destroyed by the immune system. and located either (1) between the primary lesion lesion An area of abnormal tissue that may be either benign or malignant. and the draining regional lymph nodes or (2) distal to the primary lesion

Useful Resources

The AJCC 7th Edition Staging Manual has been officially replaced by the 8th Edition as of the start of 2018. However, information about the 7th system will remain on this site for reference and can be accessed here.

FAQs

How does staging work for MCC?

In general, cancers are staged according to where the cancer is in the body: local (skin only), nodal (involves the lymph nodes), or metastatic (spread elsewhere in the body). The best survival is for local stages; the poorest is in metastatic stages with nodal disease somewhere in between. In the past, there were five different staging systems for MCC, and this created confusion. The AJCC 7th Edition Staging Manual, which is the first international “consensus” staging system, will be officially replaced by the 8th Edition at the start of 2017.

What are the main differences between the 7th & 8th Editions of the AJCC Staging Systems for MCC?

It has recently been realized that MCC patients with nodal disease who have no known primary lesion do better than node-positive patients who still have a primary lesion in place.  These two categories of Stage III (nodal) disease are separated in the new system, resulting in more accurate prediction of recurrence. In the 8th Edition system, it is now necessary to note whether staging was ‘clinical’ or ‘pathologic’ (see table in 8th Edition system) for a summary.

Understand the Science

The following clinical publications and scientific research provide additional in-depth information about disease stages.

AJCC Cancer Staging Manual

On January 1, 2010, the American Joint Committee on Cancer (AJCC) adopted a new staging system for MCC. Dr. Nghiem led the MCC taskforce of the AJCC in this analysis and wrote the chapter with Dr. Bianca Lemos. The chapter is available here for download or accessible online via the link below.

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Pathologic nodal evaluation improves prognostic accuracy in Merkel cell carcinoma: analysis of 5823 cases as the basis of the first consensus staging system.

The data and analysis to create a new staging system for Merkel cell carcinoma, now used worldwide, was published in the Journal of the American Academy of Dermatology. This was based on survival data from over 5000 MCC patients and reinforced the importance of sentinel lymph node biopsy in prognosi...

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