Protocol for the Examination of Specimens From Patients With Melanoma of the Skin (2009)

The College of American Pathologists offers these protocols to assist pathologists in providing clinically useful and relevant information when reporting results of surgical specimen examinations. The College regards the reporting elements in the “Surgical Pathology Cancer Case Summary (Checklist)” portion of the protocols as essential elements of the pathology report. However, the manner in which these elements are reported is at the discretion of each specific pathologist, taking into account clinician preferences, institutional policies, and individual practice.The College developed these protocols as an educational tool to assist pathologists in the useful reporting of relevant information. It did not issue the protocols for use in litigation, reimbursement, or other contexts. Nevertheless, the College recognizes that the protocols might be used by hospitals, attorneys, payers, and others. Indeed, effective January 1, 2004, the Commission on Cancer of the American College of Surgeons mandated the use of the checklist elements of the protocols as part of its Cancer Program Standards for Approved Cancer Programs. Therefore, it becomes even more important for pathologists to familiarize themselves with these documents. At the same time, the College cautions that use of the protocols other than for their intended educational purpose may involve additional considerations that are beyond the scope of this document.This protocol applies to melanoma of cutaneous surfaces only. The 7th edition TNM staging system for melanoma of the skin of the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC) is recommended.Select a Single Response Unless Otherwise Indicated* Data elements with asterisks are not required. However, these elements may be clinically important but are not yet validated or regularly used in patient management.Procedure (select all that apply)__ Biopsy, shave (note A)__ Biopsy, punch__ Biopsy, incisional__ Excision__ Reexcision__ Lymphadenectomy, sentinel node(s)__ Lymphadenectomy, regional nodes (specify): ______ Other (specify): ______ Not specifiedSpecimen Laterality__ Right__ Left__ Midline__ Not specifiedTumor Site (note B)Specify (if known): ______ Not specifiedTumor Size (required only if tumor is grossly present)Greatest dimension: __ cm*Additional dimensions: __ × __ cm__ Indeterminate (see “Comment”)Macroscopic Satellite Nodule(s) (required for excision specimens only)__ Not identified__ Present__ Indeterminate*Macroscopic Pigmentation*__ Not identified*__ Present, diffuse*__ Present, patchy/focal*__ IndeterminateHistologic Type (note C)Malignant Melanoma__ Melanoma, not otherwise classified__ Superficial spreading melanoma__ Nodular melanoma__ Lentigo maligna melanoma__ Acral-lentiginous melanoma__ Desmoplastic and/or desmoplastic neurotropic melanoma__ Melanoma arising from blue nevus__ Melanoma arising in a giant congenital nevus__ Melanoma of childhood__ Nevoid melanoma__ Persistent melanoma__ Other (specify): ____Maximum Tumor Thickness (note D)Specify: __ mmAt least __ mm (see “Comment”)__ Indeterminate (see “Comment”)*Anatomic Level (note D)*__ I (Melanoma in situ)*__ II (Melanoma present in, but does not fill and expand, papillary dermis)*__ III (Melanoma fills and expands papillary dermis)*__ IV (Melanoma invades reticular dermis)*__ V (Melanoma invades subcutaneum)Ulceration (note E)__ Present__ Not identified__ IndeterminateMargins (select all that apply) (note F)Peripheral Margins__ Cannot be assessed__ Uninvolved by invasive melanoma Distance of invasive melanoma from closest peripheral margin: __ mm (required for excisions only) Specify location(s), if possible: ______ Involved by invasive melanoma Specify location(s), if possible: ______ Uninvolved by melanoma in situ Distance of melanoma in situ from closest margin: __ mm (required for excisions only) Specify location(s), if possible: ______ Involved by melanoma in situ Specify location(s), if possible: ____Deep Margin__ Cannot be assessed__ Uninvolved by invasive melanoma Distance of invasive melanoma from margin: __ mm (required for excisions only) Specify location(s), if possible: ______ Involved by invasive melanoma Specify location(s), if possible: ____Mitotic Index (note G)__ Less than 1/mm2Specify number/mm2: __Microsatellitosis (note H)__ Not identified__ Present__ IndeterminateLymph-Vascular Invasion (note I)__ Not identified__ Present__ Indeterminate*Perineural Invasion (note J)*__ Not identified*__ Present*__ Indeterminate*Tumor-Infiltrating Lymphocytes (note K)*__ Not identified*__ Present, nonbrisk*__ Present, brisk*Tumor Regression (note L)*__ Not identified*__ Present, involving less than 75% of lesion*__ Present, involving 75% or more of lesion*__ Indeterminate*Growth Phase (note M)*__ Radial*__ Vertical*__ IndeterminateLymph Nodes (required only if lymph nodes are present in the specimen) (note N)Number of sentinel nodes examined: __Total number of nodes examined (sentinel and nonsentinel): __Number of lymph nodes with metastases: __Number of lymph nodes with metastases identified microscopically: __Number of lymph nodes with metastases identified macroscopically: __*Extranodal tumor extension: __ *Present __ *Not identified __ *Indeterminate*Size of largest metastatic focus: __ (mm) (for sentinel node)*Location of metastatic tumor (for sentinel node) __ *Subcapsular __ *Intramedullary __ *Subcapsular and intramedullary*Matted nodes __ Present __ Not identifiedPathologic Staging (pTNM) (note O and note P)TNM Descriptors (required only if applicable) (select all that apply)__ m (multiple)__ r (recurrent)__ y (posttreatment)Primary Tumor (pT)__ pTX: Primary tumor cannot be assessed (eg, shave biopsy or regressed melanoma) (see “Comment”)__ pT0: No evidence of primary tumor__ pTis: Melanoma in situ (ie, not an invasive tumor: anatomic level I)pT1: Melanoma 1.0 mm or less in thickness, with or without ulceration (see note D)__ pT1a: Melanoma 1.0 mm or less in thickness, no ulceration, less than 1 mitoses/mm2__ pT1b: Melanoma 1.0 mm or less in thickness with ulceration and/or 1 or more mitoses/mm2pT2: Melanoma 1.01 to 2 mm in thickness, with or without ulceration__ pT2a: Melanoma 1.01 to 2.0 mm in thickness, no ulceration__ pT2b: Melanoma 1.01 to 2.0 mm in thickness, with ulcerationpT3: Melanoma 2.01 to 4.0 mm in thickness, with or without ulceration__ pT3a: Melanoma 2.01 to 4.0 mm in thickness, no ulceration__ pT3b: Melanoma 2.01 to 4.0 mm in thickness, with ulcerationpT4: Melanoma greater than 4.0 mm in thickness, with or without ulceration__ pT4a: Melanoma greater than 4.0 mm in thickness, no ulceration__ pT4b: Melanoma greater than 4.0 mm in thickness, with ulcerationRegional Lymph Nodes (pN)__ pNX: Regional lymph nodes cannot be assessed__ pN0: No regional lymph node metastasispN1: Metastasis in 1 regional lymph node__ pN1a: Clinically occult (microscopic) metastasis__ pN1b: Clinically apparent (macroscopic) metastasispN2: Metastasis in 2 to 3 regional nodes or intralymphatic regional metastasis without nodal metastasis__ pN2a: Clinically occult (microscopic) metastasis__ pN2b: Clinically apparent (macroscopic) metastasis__ pN2c: Satellite or in-transit metastasis without nodal metastasis__ pN3: Metastasis in 4 or more regional lymph nodes or matted metastatic nodes or in-transit metastasis or satellites(s) with metastasis in regional node(s)Distant Metastasis (pM)__ Not applicable__ pM1: Distant metastasis (documented in this specimen)*__ pM1a: Metastasis in skin, subcutaneous tissues, or distant lymph nodes*__ pM1b: Metastasis to lung*__ pM1c: Metastasis to all other visceral sites or distant metastasis at any site associated with an elevated serum lactic dehydrogenase (LDH) *Specify site, if known: ____*Additional Pathologic Findings (select all that apply)*__ Nevus remnant*__ Other (specify): ____*Comment(s): ____Optimal evaluation of melanocytic lesions requires complete excision that incorporates the full thickness of the involved lesion removed intact.1 “Shave” procedures that do not include the intact base of the lesion should be avoided. Similarly, “punch” procedures may not include intact lateral borders for assessment of symmetry and lateral circumscription, which can be essential for distinction of melanoma from melanocytic nevus.23The use of frozen sections in biopsies or excisions of melanocytic lesions is strongly discouraged.4 Optimal histologic evaluation of cutaneous melanoma requires well-cut, well-stained hematoxylin-eosin (H&E) sections prepared from formalin-fixed, paraffin-embedded tissue. Frozen sections of sentinel lymph nodes are similarly discouraged because the manipulation required for intraoperative handling may decrease the sensitivity of the procedure.5For cutaneous melanoma, prognosis may be affected by primary anatomic site.67The (modified) World Health Organization (WHO) classification7 of variants of malignant melanocytic neoplasms of the skin includes the following:Superficial spreading melanomaNodular melanomaLentigo maligna melanomaAcral lentiginous melanomaMucosal-lentiginous melanomaDesmoplastic/neurotropic melanomaMelanoma arising from blue nevusMelanoma arising from a giant congenital nevusMelanoma in childhoodNevoid melanomaPersistent melanomaMelanoma, not otherwise classifiedThe WHO list is not exhaustive; this checklist does not preclude use of other diagnostic terms, for example, mucosal lentiginous melanoma, a form commonly observed in the vulva.There is ongoing research to correlate molecular abnormalities in malignant melanoma, particularly BRAF mutations, with histologic parameters. Given the wide variety of reported mutations in melanoma8 and the lack of predictably effective, targeted molecular therapy,9 practical application of such morphologic correlates remains an issue for future checklists.Maximum tumor thickness is measured with a calibrated, ocular micrometer at a right angle to the adjacent normal skin. The upper point of reference is the granular layer of the epidermis of the overlying skin or, if the lesion is ulcerated, the base of the ulcer. The lower reference point is the deepest point of tumor invasion (ie, the leading edge of a single mass or an isolated group of cells deep to the main mass).If the tumor is transected by the deep margin of the specimen, the depth may be indicated as “at least __ mm” with a comment explaining the limitation of thickness assessment.Clark levels are defined as follows:I Intraepidermal tumor onlyII Tumor present in but does not fill and expand papillary dermisIII Tumor fills and expands papillary dermisIV Tumor invades into reticular dermisV Tumor invades subcutisClark levels were previously a primary requirement for subclassifying pT1 lesions according to the AJCC 6th edition TNM classification system and are commonly reported. Anatomic level has been replaced by mitotic rate in the AJCC 7th edition tables for subclassifying pT1 lesions as T1a or T1b, but in the text and in a table comment of the AJCC chapter,10 Clark level IV or V is referred to as a tertiary criterion for T1b in cases with no ulceration and “if mitotic rate cannot be determined.” Clark level should, therefore, be reported whenever it would form the basis for upstaging T1 lesions.The distinction of T1a versus T1b is of significant clinical importance because the AJCC recommends that sentinel node examination be considered for melanomas stage T1b and above.Ulceration is a dominant prognostic factor in cutaneous melanoma without metastasis,6 and if present, changes the pT substage. The presence or absence of ulceration must be confirmed on microscopic examination.11 Melanoma ulceration is defined as the combination of the following features: full-thickness epidermal defect (including absence of stratum corneum and basement membrane); evidence of reactive changes (ie, fibrin deposition, neutrophils); and thinning, effacement, or reactive hyperplasia of the surrounding epidermis in the absence of trauma or a recent surgical procedure. Ulcerated melanomas typically show invasion through the epidermis, whereas nonulcerated melanomas tend to lift the overlying epidermis. Overall, for patients with stage I and II melanomas, the 10-year survival rate is 50% if the tumor is ulcerated and 78% if the tumor is not ulcerated.12 In Cox regression analyses of prognostic factors in cutaneous melanoma that include ulceration, a significantly worse prognosis and a higher risk of metastatic disease have been demonstrated for ulcerated versus nonulcerated tumors of equivalent thickness.611There is a positive correlation between ulceration and thickness. For ulcerated tumors, the median thickness has been shown to be about 3 mm; for nonulcerated tumors, it is about 1.3 mm. Nevertheless, the adverse prognostic significance of melanoma ulceration has been shown to be independent of tumor thickness. For thin melanomas (1.0 mm or less in thickness), level of invasion is more predictive of survival outcome than ulceration. For melanomas greater than 1.0 mm, ulceration is more predictive than thickness.6 Recent studies suggest that ulceration may lose its independent prognostic significance when mitotic rate is taken into account.13Microscopically measured distances between tumor and labeled lateral or deep margins are appropriately recorded for melanoma excision specimens because these neoplasms may demonstrate clinical “satellitosis.” Nevertheless, a “safe minimum” margin has not been established in the literature. If a lateral margin is involved by tumor, it should be stated whether the tumor is in situ or invasive.A mitotic rate of 1 or more mitotic figure per square millimeter is a powerful, adverse prognostic factor for cutaneous melanoma13 and will upstage pT1 lesions from pT1a to pT1b in the 7th edition of the AJCC staging system. The mitotic index should be reported as the number of mitoses per square millimeter. If no mitoses are found or if the average count is less than 1, the mitotic count is reported as less than 1/mm2. (Typically a 10× ocular and a 40× objective will yield a field area of approximately 0.15 mm2, but that will vary from microscope to microscope and should be determined on an individual basis by direct measurement of the field or from manufacturer's specifications.)The recommended approach to enumeration of mitoses is to, first, find the area in the vertical growth phase containing most mitotic figures, the so-called hot spot. After counting the mitoses in the hot spot, the count is extended to adjacent fields until an area corresponding to 1 mm2 is assessed. If no hot spot can be found and mitoses are randomly scattered throughout the lesion, then several different, randomly chosen areas should be counted, summed, and the average listed as the mitotic rate. In tumors where the invasive component is less than 1 mm in area, an attempt may be made to extrapolate a rate per square millimeter.Microsatellitosis is defined as the presence of tumor nests greater than 0.05 mm in diameter in the reticular dermis, panniculus, or vessels beneath the principal invasive tumor but separated from it by at least 0.3 mm of normal tissue on the section in which the Breslow measurement was taken.14See also note O.At least one study15 has suggested that vascular invasion by melanoma correlates independently with worsened overall survival.Perineural invasion may be seen in melanoma, particularly desmoplastic-neuroid subtypes.7 This feature may correlate with an increased risk for local recurrence. It is suggested that the presence of perineural infiltration be noted in surgical pathology reports on melanomas.A paucity of tumor-infiltrating lymphocytes is an adverse prognostic factor for cutaneous lymphocytes may be assessed in a as defined as lymphocytes to and tumor cells of the vertical growth Lymphocytes Not No lymphocytes present, or lymphocytes present but do not tumor at Lymphocytes Lymphocytes melanoma only or not the base of the vertical growth Lymphocytes Lymphocytes the base of the vertical growth phase or the invasive component of the melanoma of regression include of tumor cells by as as of the epidermis and with and regression adverse prognostic importance in invasive melanomas, as does regression involving more than 75% of the prognostic significance of histologic is less significant than the growth and depth of infiltration by histologic For example, spreading melanomas, by demonstrate growth and have a prognosis than melanomas, which demonstrate vertical Tumor a and is than it is commonly criterion is presence of melanoma in situ 3 or more beyond the invasive growth phase is an adverse prognostic factor for cutaneous Nodular melanomas by vertical growth in spreading melanoma is defined as the presence of 1 or more than the largest epidermal and/or the presence of any mitotic in the of sentinel lymph nodes may be for patients with cutaneous melanomas with a thickness of 1 mm or and recent that it also may be for lesions less than 1 mm of sentinel lymph node metastasis is about to in so-called thin melanomas versus about for melanomas mm of sentinel lymph nodes is not of the from levels through sentinel lymph nodes the sensitivity of microscopic melanoma sections of the surfaces of a lymph node) may to a rate of to The use of (eg, for or the sensitivity of of microscopic melanoma metastases and should also be considered in the examination of sentinel lymph should be used in and not in histologic identified are as greater than disease by the 7th edition of the AJCC staging histologic whether for sentinel node or for regional lymph node the tissue for research should be For lymph nodes may be or at whereas nodes may be number of have suggested the sentinel lymph node tumor or the of metastasis in the sentinel node as the may be useful in patients have additional disease in nodes and would patients might from complete lymph node have suggested that the or of the disease in the sentinel node may also as a prognostic If such results are validated and found to be then may be an issue for future not required for AJCC Cancer the and of tumor present in a positive sentinel are as elements in this TNM Staging of the AJCC and the is recommended by this in the 7th edition AJCC Cancer Staging of importance to pathologists staging includes of the primary melanoma and information about the regional lymph nodes or complete all studies of cutaneous melanoma, tumor thickness has been shown to be a dominant prognostic and it the basis for the of Clark levels are also commonly used to depth of invasion by the primary but are less predictive of clinical outcome than mitotic the to a primary tumor that has not been previously The to the classification of the as to the clinical and is on and microscopic examination of removed pT a of the primary tumor or biopsy to the pT of nodes to lymph node and examination of distant (microscopic) assessment of the primary tumor is required for Therefore, excision of the primary tumor, than is The classification of melanoma is on the thickness of the primary tumor, presence or absence of ulceration, mitotic in its anatomic level of invasion (see also and regional lymph nodes are the most sites of The use of cutaneous and sentinel lymph node biopsies has the to the presence of lymph node the regional lymph nodal metastasis to disease to 1 nodal or to 2 nodal as in patients with nodal disease in of or or Metastasis to nodal is considered Tumor and Lymph The edition of this checklist the use of to that for The 7th edition staging system nodal by the presence of any tumor of or of lymph node and evaluation may be in the surgical approach to cutaneous sentinel lymph node is defined as the node to from a primary may be more than one sentinel node for The clinical for sentinel lymph node and evaluation is on the that metastatic of a sentinel node the that more distant nodes may also metastatic if sentinel nodes are found to be other regional nodes would be less to all studies Cox regression the number of regional lymph nodes containing or the of regional nodes containing more strongly outcome than the of with one involved lymph node have survival than patients with any combination of 2 or more involved of the of the In their of reported the AJCC Melanoma Staging Committee found no evidence that the of lymph node metastases was an independent of is used in the 7th edition AJCC staging system for of by 2 of the primary metastasis is defined as intralymphatic tumor in skin or subcutaneous tissue more than 2 from the primary tumor but not beyond the regional lymph node The presence of in-transit metastasis between the primary tumor and the regional lymph nodes a presence of clinical or microscopic lesions a primary melanoma and in-transit metastases a and an of the by the AJCC Melanoma Staging Committee no significant in survival between the of which are associated with a prognosis equivalent to lymph node has been from the Unless is clinical or evidence of distant the stage is as clinical (ie, no distant should only be reported when metastases have been by that and should not be reported by the of cases of TNM or the and a are do not the stage cases stage the of the disease for patients of includes or surgical or when or is the primary with no surgical The of disease is the same and and is identified as with a or classification is used because information from procedures and from of disease defined clinically may be prognostic for patients with a It is important to that the classification does not the clinical or staging of the classification is used to stage cases of not and only in a patient with (eg, surgical for is by a system as as of tumor cannot be No the the classification may be useful to the or of the of a surgical For the pathologist, the classification is relevant to the of the margins of a surgical tumor involving the margin on examination may be to to tumor in the patient and may be as or microscopic according to the at the specimen invasion whether microscopic invasion is identified in the pathology report. includes vascular or does not the local of tumor, in the of a from studies have suggested that an elevated serum level of is a prognostic factor for survival in In these has been defined as serum levels greater than to or as levels elevated the reference of the reference It is recommended that any reference be by at least For stage IV melanoma, a serum level has also been shown to be an adverse prognostic