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Histopathology Criteria

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Histopathology Criteria

What do the words on the pathology report mean?

Once the lesion is removed, the tumor or specimen is then sent to the pathology lab for dissection and microscopic examination of the tissue cells. Histopathological criteria include tumor thickness, anatomic skin depth of tumor invasion (Clark’s Level), presence of absence of ulceration, cell type, angiogenesis, vascular invasion, microsatellites, mitotic rate, and number of tumor infiltrating lymphocytes. These criteria are used in staging the melanoma and allow medical professionals to prioritize the most appropriate treatment and follow up care. As of June 2002, the American Joint Cancer Committee (AJCC) reformulated the pathologic staging system for melanoma based on several large-scale studies and updated research.

Tumor thickness or Breslow’s scale has long been the gold standard as the single most important prognostic determinant for primary melanomas. However, a positive sentinel lymph node may become the best prognosticator as the results of more SNLB studies are finalized. Tumors are currently measured by an ocular micrometer from the base of the tumor to the stratum granulosum and reported in millimeters (mm). Thin tumors measure less than or equal to 1mm, intermediate tumors measure 1.01-2.0 mm, moderate tumors measure 2.01-4.0 mm, and thick tumors are greater than 4.01 millimeters. Generally, thin tumors have a better prognosis than thick unless they are accompanied by additional histological criteria, especially a deeper level of skin invasion. Thus, in Stage I tumors, a Clark’s level of IV or V is a more critical marker of disease penetration than tumor thickness. This is not true of thicker tumors where the level of skin invasion is less pertinent.

Anatomic skin depth of tumor invasion is the definition of Clark’s Levels. The skin is divided into five levels from little penetration to deep infiltration based on the skin layer affected. Level I is non-invasive and only in the epidermis. Level II is partial invasion of the papillary dermis. Level III is full invasion of the papillary dermis. Level IV is invasion into the reticular dermis. Level V is invasion into the subcutaneous tissue. Levels IV and V are critical because they contain lymphatic and circulatory vessels which can spread the tumor cells throughout the body. Clark’s level is an important prognostic indicator in melanomas less than 1 mm but loses significance with thicker lesions.

The presence of ulceration is a new criterion for 2002. Ulceration is found less often in thin melanomas and increases in incidence with thicker tumors. Multiple studies have shown that ulceration is associated with a poorer outcome and is thought to be a sign of a more rapidly developing melanoma. In a study conducted of 17,600 melanoma patients, ulcerated tumors had the same survival rate as melanomas in the next higher tumor classification without ulceration (Balch, 2001).

Cell types of melanoma are discussed in greater detail under the Melanoma Types section. Five primary types are described – superficial spreading, nodular, lentigo maligna, acral lentiginous, and amelanotic melanoma. Suffice it to say that nodular melanoma has no radial growth phase, only a vertical growth phase, and as such, is the fastest growing of all the types. Superficial spreading and lentigo maligna often have long horizontal growing stages before they develop a vertical growth component and thus often have a better prognosis if they are removed earlier. Acral lentiginous has a tendency to recur locally and also has a shorter interval to recurrence (Wells, 1992).

Angiogenesis and vascular invasion respectively allow the tumor to both grow and spread. Angiogenesis is the formation of new blood vessels. Vascular invasion means that tumor cells have penetrated the blood vessels. The lack of angiogenesis and vascular invasion even in thick melanomas has been associated with longer survival times.

Microsatellites are small groups of tumor cells measuring at least 0.05mm in diameter and distanced from the main tumor. Presence of these indicates an increase in lymph node metastasis and local recurrence. In the 2002 staging system, the existence of microsatellites places the patient in the N2c stage of the TNM system.

Mitotic rate is a measurement of how quickly the cells are replicating and is recorded as the number of mitotic figures observed per millimeter squared of invasive tumor. A mitotic rate of zero is good. Higher rates correlate with a greater risk of metastasis. It has been postulated that a higher mitotic rate may represent tumor clones with a faster rate of reproducing and a stronger risk of metastasizing. Combined with tumor thickness it has a high importance.

When a tumor grows, the body’s immune defense system creates lymphocytes that infiltrate the tumor base and produce an inflammatory response to fight off the abnormal cells. This response is labeled TIL for Tumor Infiltrating Lymphocytes. This lymphocytic infiltration is measured and categorized as brisk, non-brisk, or absent. The higher the TIL response, the better the prognosis. Brisk is better than non-brisk which is better than absent. Thinner tumors usually have a higher TIL response than thicker tumors. It represents the body’s ability to fight off the tumor.