Pathology

Path To Getting a Pathology Diagnosis

Skin samples taken by a biopsy or surgical excision are typically sent to a pathologist/pathology laboratory for microscopic examination and diagnosis. A pathology report is issued by the pathologist or dermatopathologist, (a pathologist who specializes in skin biopsies). The pathology report states the diagnosis and further describes many aspects of the appearance of the melanoma, including the type, depth of invasion, tissue level of invasion, presence or absence of a lymphatic response, presence or absence of ulceration, mitotic count, presence or absence of regression, presence or absence of satellite lesions, and presence or absence of blood vessel/lymphatic vessel/nerve invasion.

Additionally, the pathology report will describe whether the excised lesion is a primary melanoma, in which case it would be described using the terms above, or a metastatic melanoma deposit. A metastatic melanoma deposit is one in which the melanoma started somewhere else on the skin and some of the melanoma cells broke off and spread within the skin tissue to the current biopsy/specimen site.

Some Terms You May See on Your Pathology Report

Histologic subtype (the type of melanoma):

  • Superficial spreading melanoma
  • Nodular melanoma
  • Acral lentiginous melanoma
  • Lentigo melanoma
  • Desmoplastic melanoma
  • Other: mucosal melanoma
  • Other: uveal melanoma

Breslow Depth: Measurement in millimeters of how thick the primary tumor is, regardless of its Clark Level. It is measured from the top layer of the skin to its deepest point.

Clark Level: A description of how deeply the primary tumor penetrates into the layers of the skin. Clark levels include I to V, (see layers below). Clark Level was replaced in the revised melanoma staging system in 2010 by more reliably predictive features (mitotic count and ulceration). It is now only used for non-ulcerated tumors

  • Clark Level I-lesion involves the epidermis
  • Clark Level II-lesion involves the papillary dermis
  • Clark Level III-lesion invades and fills the papillary dermis
  • Clark Level IV-lesion invades reticular dermis
  • Clark Level V-lesion invades subcutaneous tissue

Depending upon where the melanoma is located on the body, the thickness of the skin can differ, thus, the same thickness of melanoma can have different levels depending upon a person’s skin thickness and location on the body.

Radial Growth Phase (RGP): The melanoma lesion is described as either having RGP present or absent. If present, RGP indicates that the melanoma is growing horizontally, or radially, within a single plane in the upper/superficial skin layers (mainly in the epidermis).

Vertical Growth Phase (VGP): The melanoma is described as either having VGP present or absent. If present, VGP is an indication that the melanoma is growing vertically, or deeper, into the tissues.

Tumor-Infiltrating Lymphocytes (TILs): TILs describe the patient’s immune response to the melanoma. When the pathologist examines the melanoma under the microscope, he looks to see whether or not there are lymphocytes within the melanoma. The amount of lymphocyte invasion/response to the melanoma is described as brisk (a lot of lymphocytes), nonbrisk (some), sparse (few) or absent (none), although occasionally it can be described as mild or moderate. TILs appear to indicate that your immune system has recognized the melanoma cells as abnormal and is trying to move into the melanoma to attack it. Some studies suggest that the presence of increasing number of TILs may be associated with a better prognosis.

Ulceration: Ulceration is described as being present or absent. It is the breakdown or loss of the top layer of cells in a melanoma and often occurs in the center of a tumor. The presence of ulceration increases the stage classification of a melanoma. Ulceration is thought to reflect rapid tumor growth, leading to the death of cells in the center of the melanoma and thus is associated with a worse prognosis. The pathologist can determine whether ulceration is present or absent when they review the biopsy under the microscope.

Regression: Regression is described as an area of the tumor without active melanoma cell growth and is described as present or absent. If it is present, the extent of regression is estimated.. When regression is present, the measured thickness of the melanoma may not be the greatest/true thickness.

Mitotic Count (Mitotic Rate): Mitosis is the process by which one mature cell divides into two identical cells. When pathologists study a melanoma they will count the number of actively dividing cells that they see. Averaging this number gives the mitotic count and it is reported as the number of mitoses per square millimeter (mm2), (example ≤1 mitoses/mm2). A high mitotic count means more tumor cells are dividing at a given time, and is associated with a worse prognosis.

Satellites: Satellite lesions are small nodules of tumor/melanoma located more than 0.05 mm from the primary lesion, but less than 2 cm. Satellites are described as being present or absent. Satellite lesions can be seen on the pathology report (microscopic) as well as with the naked eye (macroscopic). Satellite lesions are associated with a worse prognosis.

Blood Vessel/Lymphatic Invasion: Blood vessel invasion, also called angioinvasion, or lymphatic vessel invasion, is described as being present or absent. If present, it means that the melanoma has invaded the blood or lymph system and is associated with more aggressively growing melanomas.

An Example of a Melanoma Pathology Report

This is an example of a pathology report for a melanoma diagnosis. The purpose of the report is to convey the specific findings of the melanoma that support the diagnosis and to give information about prognosis to the doctor so that she/he can advise the patient on the next recommended steps in workup and treatment.

Date of Biopsy: The date the biopsy was submitted

Submitting Service/Physician: Your doctor

Accession #: A number assigned to the biopsy specimen

Patient: Your name

Sex: Your gender

DOB: Your birthday

MRN: A medical record number

Clinical History: A description by your physician of the lesion that was biopsied. Usually a doctor will include size, location, and what he is concerned about. (Example: a 7-mm eroded pigmented papule from the left upper back. Please rule out an atypical melanocytic nevus vs. melanoma.)

Gross: A description of the actual size of the biopsied tissue and what it looked like to the naked eye. This is used by the pathologist for identification of the tissue. (Example: One container of formalin, labeled with the patient’s name, and MRN, which contains a bisected skin shave, 5 mm depth x 12 mm diameter. The epidermis is wrinkled, pink-tan, with areas showing purple preoperative ink)

Diagnosis: A summary of the findings and a diagnosis. (Example: MALIGNANT MELANOMA, 2.4mm in thickness, ulceration not seen)

Description: A description of the appearance of the biopsy under the microscope. There are specific features that are typically commented upon. (Example: A shave of skin demonstrates epidermal ulceration overlying a collection of irregular melanocytes. There is pagetoid spread of melanocytes into the epidermis. Multiple bizarre nuclei are appreciated. There are nests of atypical melanocytes extending down into the dermis without normal maturation.)

Additional Features: In the case of melanoma, pathologists will specifically comment on features that are relevant for prognosis and treatment. These are sometimes included in the description but also may be in list form as shown below:

Diagnosis: Malignant Melanoma

Tumor site: Location on the body from which the biopsy was taken

Histologic type: Superficial spreading, nodular, lentigo maligna, acral lentiginous, desmoplastic or unclassified

Level of invasion (Clark Level): Describes how deeply the primary tumor has penetrated into the layers of the skin. Clark levels include I to V, with I being the most shallow in the epidermis and V the deepest, in the fatty tissue under the skin. Clark Level was replaced in the revised melanoma staging system in 2010 by more reliably predictive features (mitotic count and ulceration.) It is now only used for non-ulcerated tumors

Growth phase: Radial growth phase (present or absent) Vertical growth phase (present or absent). This describes whether the melanoma has begun an invasive pattern.

Greatest thickness: Also known as Breslow thickness, it describes in millimeters the thickest part of the melanoma. It is very important for prognosis. A thinner tumor has a better prognosis.

Mitotic count: Mitosis is the process by which one mature cell divides into two identical cells. The pathologist counts the number of actively dividing cells (mitoses) that they see. This is seen in many cancers, including melanoma. Averaging this number gives the mitotic count, which is stated as the number of mitoses per square millimeter (mm). Most often this count is reported as:

  • Less than or equal to 1 per square millimeter
  • Or the actual number is provided

A higher mitotic count means more tumor cells are dividing at a given time and is associated with a worse prognosis.

Tumor infiltrating lymphocytes (TILs): Lymphocytes are immune cells. Lymphocytes can be present in a melanoma and are described as “brisk,” “nonbrisk,” “sparse”, and “absent.” A brisk immune response has been associated with a better prognosis. However, the true significance of this criterion is still controversial, and some pathologists do not report it.

Regression: Refers to an area of the tumor without active melanoma cell growth and is thought to be evidence that some of the melanoma was destroyed by one’s immune system. There are conflicting reports on whether this finding has useful prognostic significance. Historically, regression has been associated with a worse prognosis.

Ulceration: The breakdown or loss of the top layer of the skin (the epidermis.) The presence or absence of ulceration is determined by the pathologist when he reviews the specimen under the microscope. Having ulceration is associated with a worse prognosis. Patients who report bleeding from their melanoma often have ulceration in the biopsy.

Satellite lesions: Also called “local metastasis.” They are small nodules of melanoma located more than 0.05mm from the primary lesion but less than 2cm. They are described as being present or absent. Satellite lesions can be seen on the pathology report (microscopic) as well as with the naked eye (macroscopic). Satellite lesions are associated with a worse prognosis.

Blood Vessel / Lymphatic invasion: Evidence that melanoma cells have entered the blood vessels or lymphatic system. The presence of this finding is associated with a worse prognosis.

Neural invasion: Evidence that melanoma cells are entering the local nerve fibers. The presence of this finding is associated with a worse prognosis.

Margins: Margins are the edge of a biopsy or surgical excision specimen. If melanoma extends to the edge of the sample (the margins), then it is presumed that the biopsy or excision did not remove the entire tumor. Deep margins are located at the base of the biopsy/specimen and lateral margins are the side edges of the biopsy/specimen. If there is no tumor extending to the margins, the pathologist will describe how close the lesion came to the edge. (Example: tumor extends to within 2 mm of the margin). The thickness of the melanoma primary is used to guide the recommended margin of normal tissue the surgeon plans to remove at the time of surgery.

Recommendations: Based on all the above information, the pathologist may make initial recommendations to the doctor, including whether another biopsy needs to be done to get additional tissue, or whether the doctor should perform an excision of the lesion to ensure complete removal.

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