Guide Pathology of Malignant Melanoma

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Other histologic variables associated with a poor prognosis include ulceration, diminished lymphoid response, evidence of tumor regression, microscopic satellites, lymphovascular invasion, and non—spindle-cell type tumors. Patients with nodal micrometastases have an improved survival compared with patients with clinically palpable nodes.

Patients with melanoma on an extremity and younger age at diagnosis have been shown to have a better prognosis. If there are distant metastases, median survival is about 6 to 9 months. In order to offer the best counseling to patients, all data related to the tumor must be synthesized into as precise a stage as possible. All data related to the tumor can be used to group patients into one of several clinical stages, as shown in Table 2. Conventionally, clinical staging should be used after biopsy of the primary tumor, with clinical assessment for regional and distant metastases.

As such, there is only 1 clinical stage for lymph node metastases and 1 stage for distant metastases. Pathologic assessment of the primary melanoma is used for both clinical and pathologic classification. A diagnostic evaluation of regional and distant metastases is included. Pathologic staging includes histologic information related to the primary tumor from biopsy and excision, and information about the regional lymph nodes after sentinel lymph node biopsy or completion lymph node dissection for clinically evident regional lymph node disease.

Source: Adapted from refernce The prognosis for a patient with localized primary cutaneous melanoma is mainly related to tumor thickness. Survival data for patients with nodal status known to be negative is shown in Table 3. Note: Thickness is defined as the thickness of the lesion using an ocular micrometer to measure the total vertical height of the melanoma from the granular layer to the area of deepest penetration. The Clark level refers to levels of invasion according to depth of penetration of the dermis. Prognosis for patients with nodal disease relates to both thickness of the primary tumor, the size and extent of metastatic deposits within the lymph node, and presence of distant metastases.

The 5- and year survival data for patients with known metastatic disease in the lymph node is presented in Table 4. Melanoma specific survival data, when combining staging data for the primary tumor, nodal disease, and the presence or absence of distant metastases, is presented in Table 5. The goal of regular follow-up of patients with melanoma is the detection of local recurrence, regional metastasis to lymph nodes, distant metastasis of the primary melanoma, or development of a second primary melanoma.

Each visit should include a detailed history and physical examination, with further testing driven by specific signs and symptoms. For most patients with stage I or II melanoma, follow-up appointments should be scheduled every 3 months for the first 2 years, then every 6 months for 3 years, then once a year thereafter. If the patient has dysplastic nevi, the interval may be continued at every 6 months indefinitely.

Given the results of the Multicenter Selective Lymphadenectomy Trial II, 34 patients with stage III melanoma who have occult disease detected only with sentinel lymph node biopsy may be followed with serial ultrasonography of the regional basin, rather than immediate completion lymph node dissection.

The optimal interval for sonographic evaluation has not been determined, although a similar interval can be used as suggested above for patients with stage I or II disease. Clinical serial photography may be helpful when following patients with multiple clinically atypical nevi. Patients should also be taught and encouraged to practice monthly skin self-examination. Many new technologies are being developed to help clinicians and patients evaluate moles.

These include handheld and computer-aided epiluminescence microscopy and ultrasound-based devices, as discussed above. Additionally, smartphone applications have been developed to store clinical photographs and enable patients to evaluate changes in their moles over time. Finally, smartphone and office-based teledermatology platforms are proving to shorten the time to diagnosis by reducing barriers to specialty care.

Primary prevention of melanoma requires reduction of known risk factors in people at risk. The most important modifiable behavior for melanoma prevention is reduction of ultraviolet exposure, both from the sun and from tanning beds. Educating the public about sun avoidance and sun protection, risk factors for developing skin cancer, and skin self-examination is essential.

Apply a broad-spectrum sunscreen with a sun protection factor SPF of 15 or higher. Reapply sunscreen every 1. Wear sun-protective clothing including a wide-brimmed hat, sunglasses, long-sleeved shirt, and long pants. Apply lip balm that contains sunscreen with an SPF 15 or higher. Seek shade while outdoors during the day. Protect children by minimizing sun exposure and by regularly applying sunscreen after the age of 6 months. Avoid tanning beds. Box 2: Clinical Differential Diagnosis of Melanoma Benign melanocytic lesion, such as nevus or solar lentigo Atypical nevus Squamous cell carcinoma Pigmented basal cell carcinoma Pyogenic granuloma Seborrheic keratosis.

Figure 1: Click to Enlarge. Figure 2: Click to Enlarge. Figure 3: Click to Enlarge. Figure 4: Click to Enlarge. Figure 5: Click to Enlarge. Figure 6: Click to Enlarge. Figure 7: Click to Enlarge. Figure 8: Click to Enlarge. Figure 9: Click to Enlarge. Table 1. TNM groups to stratify patients based on tumor characteristics, nodal disease, and Primary tumor T. Table 2. Clinical and pathologic staging groups for melanoma.

Clinical tumor, node, metastasis cTNM. Melanoma-specific survival for all stages of melanoma 5-year survival year survival Clinical stage. Back to Top Follow-up evaluation The goal of regular follow-up of patients with melanoma is the detection of local recurrence, regional metastasis to lymph nodes, distant metastasis of the primary melanoma, or development of a second primary melanoma.

Back to Top Prevention and screeening Primary prevention of melanoma requires reduction of known risk factors in people at risk. References American Cancer Society. Statistics for Accessed June 1, American Academy of Dermatology. Melanoma Fact Sheet. Skin Cancer Foundation. What is Melanoma? Determination of the impact of melanoma surgical timing on survival using the National Cancer Database. J Am Acad Dermatol ; 78 1 — Increasing incidence of melanoma among young adults: an epidemiological study in Olmsted County, Minnesota. Mayo Clin Proc ; 87 4 — Current therapy of cutaneous melanoma.

Plast Reconstr Surg ; — J Am Acad Dermatol ; — Mayo Clinic Proc ; — Tsao H. Update on familial cancer syndromes and the skin. The mitogen-activated protein kinase pathway in melanoma part I — Activation and primary resistance mechanisms to BRAF inhibition. Eur J Cancer ; — Melanoma staging: evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin ; 67 6 — Melanocytic nevi and neoplasms.

Philadelphia: WB Saunders, ;— Melanocytic nevi, dysplastic nevi, and malignant melanoma in children from melanoma-prone families.

Melanoma - Clinico-Pathologic Subtypes

J Am Acad Dermatol ; 33 4 — High risk of malignant melanoma in melanoma-prone families with dysplastic nevi. Ann Intern Med ; — Reexamining the threshold for reexcision of histologically transected dysplastic nevi. JAMA Dermatol ; 12 — Punch biopsy vs shave biopsy: a comparison of margin status of clinically atypical pigmented lesions.

Br J Dermatol ; 3 — Cutaneous melanoma risk and phenotypic changes in large congenital nevi: a follow-up study of 46 patients. Cohen LM. Lentigo maligna and lentigo maligna melanoma. Melanoma in situ: Part II. Histopathology, treatment, and clinical management. J Am Acad Dermatol ; 73 2 — Dermoscopy improves the diagnostic accuracy of melanomas clinically resembling seborrheic keratosis: cross-sectional study of the ability to detect seborrheic keratosis-like melanomas by a group of dermatologists with varying degrees of experience.

Dermatology ; 6 — Reflectance confocal microscopy features of thin versus thick melanomas. The performance of MelaFind: a prospective multicenter study. Arch Dermatol ; 2 — Ali-Salaam P, Ariyan S. Lymphatic mapping and sentinel lymph node biopsies. Clin Plast Surg ; — Predictors for use of sentinel node biopsy and the association with improved survival in melanoma patients who have nodal staging.

Ann Surg Oncol ; 25 4 — Clinical Practice Guidelines: Melanoma. National Comprehensive Cancer Network. Final trial report of sentinel-node biopsy versus nodal observation in melanoma. N Engl J Med ; 7 — Prognostic value of sentinel lymph node biopsy according to Breslow thickness for cutaneous melanoma. J Am Acad Dermatol ; 78 5 — Impact of gene expression profiling on decision-making in clinically node negative melanoma patients after surgical staging. J Drugs Dermatol ; 17 2 — Melanoma nomogram. Memorial Sloan Kettering Cancer Center.

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Melanoma Outcome Calculator. Laboratory for Quantitative Medicine. Cutaneous head and neck melanoma treated with Mohs micrographic surgery. Management of lentigo maligna and lentigo maligna melanoma with staged excision: a 5-year follow-up. Arch Dermatol ; — Completion dissection or observation for sentinel-node metastasis in melanoma. N Engl J Med ; 23 — This system utilizes the extent of the primary tumor, the absence or presence of cancer in the lymph nodes, and the existence of metastasis to assign a TNM rating, which corresponds to a stage.

In melanoma, staging is used to determine the aggressiveness of the cancer and what treatment is needed. Some pieces of the report are used to determine the stage of the cancer and other pieces play a role in deciding what treatment is needed. By understanding the basics of the report, you will be better able to discuss your treatment options with your healthcare team. Toggle navigation. Start Here! Author: OncoLink Team. Last Reviewed: September 26, What is a pathology report?

What will you find on a pathology report? Type of Melanoma Also called the histologic type or cellular type of melanoma. There are four major subtypes, with a few rare subtypes: Superficial Spreading Melanoma: most common of the melanomas. Nodular Melanoma: are always vertical growth phase present see below melanomas. Most commonly found on the chest, back, head or neck.


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Acral Lentiginous: most common type in dark skinned and Asian populations. More frequently occur on soles of feet, palms of hands or under nails. Lentigo Maligna Melanoma: tends to occur on sun-exposed areas in older people. Often found on the face or neck. Clark's Level II: lesion involves the papillary dermis.

Clark's Level III: lesion invades and fills the papillary dermis. Clark's Level IV: lesion invades reticular dermis. Clark's Level V: lesion invades sub-cutaneous tissue.

Histology of malignant melanoma

Types of Biopsies may be listed under the procedure section : Shave Biopsy: a superficial area of the lesion is taken off, often with a razor-type blade. Punch Biopsy: the removal of a circular area of skin with an instrument known as a punch, which comes in various sizes- sort of like a miniature round cookie cutter. Incisional Biopsy: the removal of a portion of the affected tissue, for examination, using a knife.

Excisional Biopsy: the removal of the entire affected area and often some healthy tissue for examination using a knife. Putting it all together Some pieces of the report are used to determine the stage of the cancer and other pieces play a role in deciding what treatment is needed. For the invasive component, both the deep and peripheral margin must be recorded separately.

The pathology report should document the:. If involved, the location s must be specified if possible. If not involved, the distance of the melanoma from the closest uninvolved margin must be recorded, and the location s of the closest uninvolved margins should be recorded, if possible. It was recommended that margin measurements to within the nearest 1 mm are sufficient for the purposes of directing further management. If the melanoma is within 2 mm of the resection line, it is 34 recommended that the margin measurement be recorded to within the nearest 0.

The standard treatment for primary melanoma is wide local excision of the skin and subcutaneous tissues around the melanoma. Such definitive treatment is not usually performed until after a pathologic diagnosis of melanoma has been established. The aim is complete surgical excision of all in situ and invasive melanoma components. Involvement of the surgical margin may result in regrowth or metastasis from residual melanoma and may adversely affect patient outcome.

Clinically measured wide excision margins are a less precise measure of the extent of excision of normal tissues surrounding the tumor than the histopathologic margins. However, there is very little evidence available for the relationship between histopathologic measured margin and local, in-transit, and regional recurrence. Providing data on distance of melanoma from the margins may be helpful not only to clinicians in guiding patient management but also for pathologists when examining any subsequent specimen eg, reexcision specimen or for determining whether recurrent tumor at the primary site represents local persistence of melanoma or a metastasis.

Defining the peripheral extent of the epidermal component of a melanoma may be difficult and subjective particularly for melanomas arising in chronically sun-damaged skin in which the peripheral changes merge with those related to the effects of severe chronic sun damage and also for acral and mucosal melanomas.

The ABCDE's of Melanoma

Assessing the presence of ulceration may be difficult in recently biopsied lesions and in cases in which there is only a focal loss of the epidermis; in this case, it is difficult to determine whether the epidermal deficiency is due to ulceration or to sectioning artifact. Absence of fibrin or granulation tissue from putative areas of ulceration would be clues that the apparent ulceration is actually due to sectioning of only part of the epidermis. Multiple studies indicate that mitotic count is an important prognostic factor for localized primary melanomas including very large studies utilizing the methodology for mitotic count determination described below.

The number of mitotic figures can vary greatly between different parts of a tumor. For consistency and reproducibility, a standardized method must be used to assess mitotic count. If no hot spot is identified and the mitotic figures are sparse and randomly scattered, then the count should begin in a field containing a mitosis, then extended to immediately adjacent nonoverlapping high-power fields until a 1 mm 2 area of tissue containing melanoma is assessed. It is also recommended in the seventh edition of the AJCC staging manual that the mitotic count should be assessed in all primary melanomas for prognostic purposes.

The data that demonstrated the strong prognostic significance of mitotic count were obtained from the melanoma pathology reports of routinely assessed hematoxylin and eosin-stained sections. It is therefore not recommended that any additional sections be cut and examined or immunochemical analysis be performed , in excess of those that would normally be used to report and diagnose the melanoma , to determine the mitotic count ie, no additional sections should be cut and examined for the purpose of determining the mitotic rate; this includes the situation when no mitotic figures are identified on the initial, routinely examined sections.

Vascular invasion is identified by the demonstration of melanoma cells within the lumina of blood vessels or lymphatics or both. It is an uncommon finding in the excision specimens of primary cutaneous melanoma but is generally regarded as a marker of poor prognosis. Neurotropism is identified by the presence of melanoma cells around nerve sheaths perineural invasion or within nerves intraneural invasion. Infiltration along nerve sheaths or occasionally within the endoneurium may be associated with an increased local recurrence rate local persistence.

A microscopic satellite is any nest of metastatic tumor cells discontinuous from the primary tumor but not separated only by fibrosis or inflammation. The presence of a melanoma satellite metastasis at a peripheral excision margin may be an indication for reexcision, because it implies that there may be further melanoma in the skin beyond the visible margins.

Desmoplastic melanoma is a rare subtype of melanoma characterized by malignant spindle cells separated by prominent fibrocollagenous or fibromyxoid stroma. Similar findings have since been reported by others. The committee considered that if lymph nodes are NOT received, this element should not be reported. Tumor-harboring status of the SLN is the strongest predictor of outcome for clinically localized primary cutaneous melanoma patients.

There are a number of potential pitfalls in the microscopic examination of SLNs. This can usually be resolved by careful assessment of the location, morphologic features, and immunohistochemical staining characteristics of the cells and, in some instances, comparing the cytology of the nodal melanocytes with the cells of the primary invasive melanoma. These can usually be distinguished from melanoma cells on the basis of their location, size, shape, nuclear and cytoplasmic characteristics, distribution within the node, and immunohistochemical profile.

In our experience, the occurrence of such cells has become a more frequent diagnostic problem in recent years, presumably reflecting the utilization of more sensitive antibodies and immunohistochemical techniques. Similarly, weak positive staining for HMB is sometimes observed in pigment-laden macrophages. Lymph node positivity is defined by the presence of melanoma cells identified on hematoxylin and eosin-stained sections or on sections stained by immunohistochemistry alone.

Other criteria for the N category are satellites, in-transit metastases, and microsatellites. M staging continues to be determined both by the site of distant metastases and serum lactate dehydrogenase, but patients with regionally isolated metastasis from an unknown primary site should be categorized as stage III rather than stage IV, because their prognosis corresponds to that of stage III disease from a known primary site.

Pathologic assignment of the presence of metastasis pM1 requires a biopsy positive for cancer from a metastatic site. Other lesions are often nevi or other benign lesions, but it is particularly important to identify the presence of satellite metastases because these portend a worse prognosis. Table 3. The common melanoma subtypes superficial spreading melanoma , nodular melanoma , and lentigo maligna melanoma have little, if any, prognostic significance independent of tumor thickness, interpretation is subjective and prone to interobserver variation, 4,18,95—97 and their use is principally for clinicopathologic correlation.

Nevertheless, the traditional Clark melanoma histogenetic classification highlights the myriad of clinical and histologic guises of melanoma , which if not recognized by clinicians and pathologists will potentially lead to a delay in diagnosis and a concomitant adverse clinical outcome. Epidemiological and molecular genetic evidence suggests that there are subgroups of melanoma that are associated with specific genetic alterations. There are associations between the presence of some mutations and the anatomic site of a melanoma and the degree of solar elastosis.

For example, melanomas associated with prominent solar damage lentigo maligna melanomas commonly have NRAS and sometimes KIT mutations, whereas superficial spreading melanomas that arise in the skin of intermittently sun-exposed areas often have BRAF mutations. KIT -mutated melanomas most often involve acral acral-lentiginous melanoma and mucosal sites.

Nevertheless, the degree of accuracy of the melanoma histogenetic subtype or histopathologic assessment for predicting the mutation status of a melanoma is not sufficient to replace mutation testing for the purposes of patient care. Extent of ulceration measured either as diameter or percentage of tumor width provides more accurate prognostic information than the mere presence of ulceration. As discussed above, Clark level may also provide useful prognostic information if an accurate Breslow thickness cannot be determined.

Most evidence suggests that the Breslow thickness of a melanoma is a more accurate prognostic indicator than the Clark level. The assessment and grading of TILs remains subjective and prone to interobserver variation, although agreement may be improved by instruction. A host immunologic response may be directed against melanoma cells and may result in elimination of part or all of the melanoma ; this is termed regression. This phenomenon may be categorized into 3 temporal stages: early, intermediate, and late. Early regression is signified by the presence of TILs.

Intermediate and late regression result in partial or complete loss of melanoma and are characterized by immature intermediate and mature late dermal fibrosis, often accompanied by the presence of melanophages and effacement of the rete architecture. Most reports assessing the prognostic significance of regression have not differentially analyzed intermediate and late regression.

The prognostic significance of intermediate and late regression is controversial. Regression at a peripheral excision margin is an indication for reexcision, because it probably implies that there may be further melanoma in the skin beyond the visible margins. Although of no known prognostic value, the recognition of an associated benign melanocytic lesion is relevant to the pathogenesis of melanoma and may be important for clinicopathologic correlation and epidemiological, clinical, and genetic studies.

In some instances, it can be difficult or even impossible to determine whether part of the dermal component of a melanocytic tumor represents melanoma or an associated nevus. Histologic parameters of melanoma deposits in SLNs have been shown to be predictive of the presence or absence of tumor in non-SLNs and clinical outcome. However, if there are multiple large deposits of melanoma cells that extend deeply into the central part of an SLN, the prognosis is much worse, and the chance of finding additional metastases in non-SLNs in a completion lymph node dissection specimen is much higher.

SLN parameters predictive of non-SLN status and survival include the size of metastases, tumor penetrative depth also known as maximal subcapsular depth and centripetal thickness and defined as the maximum distance of melanoma cells from the nearest inner margin of the lymph node capsule , the location of tumor deposits in the SLN, the percentage cross-sectional area of the SLN that is involved, and the presence of extracapsular spread.

However, the power of individual features of melanoma metastases in SLNs to predict tumor in non-SLNs, as well as survival, reported in some studies has not been reported by others. The determination of some of these parameters may not always be reliable, because tumor deposits are often irregularly shaped, the limits of tumor deposits can be difficult to discern, and tumor burden is to some degree dependent on sectioning protocols, as more extensive sectioning may reveal additional tumor deposits or demonstrate a greater dimension of deposit s in the deeper sections.

The pathology report is critical in determining the management of patients with primary cutaneous melanoma. Melanoma patients with suboptimal pathology reports may be staged inadequately, managed poorly, and thus may ultimately experience an adverse clinical outcome. Clear communication between pathologists and clinicians is essential. The use of a structured report with predefined data elements and acceptable response values can facilitate this communication. It not only helps to ensure completeness of pathology reports but also consistency in reporting.

Further, the stipulation of acceptable predefined values can save time for the person completing and typing the report. In addition, a structured pathology report facilitates efficient extraction of information for registries, data collection, and research purposes. It should be emphasized that, although structured pathology reporting provides the framework for the minimum set of features to be assessed, it by no means restricts the pathologist to documenting only those features.

All structured pathology reports must include the facility for free text comments. For melanocytic lesions that are difficult to classify as either a melanoma or a nevus and also for quality assurance purposes, the inclusion of a narrative element in a pathology report is useful, because it documents the histopathologic features used to justify a diagnosis and can provide a description of any difficulties encountered in assessing microscopic features. For melanocytic lesions that are difficult to classify, we recommend that the evidence in favor and against the particular diagnosis be presented and a preferred or favored diagnosis be provided, along with the degree of uncertainty.

If a malignant diagnosis is favored, the structured report template may also be completed. In doing so, it will be important that although additional items may be included according to local needs, the required and recommended elements listed above must retain the same naming conventions, units of measurement, value lists, and methods of assessment if valid comparisons are to be made throughout the world. It is important to note that any pathology reporting protocol will require modification from time to time as new scientific data emerge. New prognostic markers in melanoma patients such as tumor necrosis are regularly reported and once validated in independent data sets may warrant inclusion in future versions of this protocol.

However, at present, there are no ancillary tests currently used on a routine diagnostic basis for primary cutaneous melanoma. For most melanomas, immunochemistry is not required to establish a pathologic diagnosis of melanoma. Nevertheless, in some instances it eg, HMB and Ki labeling may be helpful in determining whether a primary melanocytic tumor is benign or malignant. With the recent development and testing of new promising targeted therapies for patients with metastatic melanoma , — molecular pathology mutation testing for BRAF , NRAS , KIT , and other mutations has become common in many melanoma treatment centers.

At the present time, routine mutation testing is recommended only in patients with inoperable AJCC stage III or stage IV disease and will therefore usually not be performed at the time of diagnosis of primary cutaneous melanoma , and mutation testing was not included in the current version of the ICCR melanoma pathology reporting protocol. In conclusion, this manuscript describes the process and evidentiary review in the development of the ICCR cutaneous melanoma pathologic reporting protocol.

In addition, to minimize ambiguity and to facilitate electronic implementation, the protocol specifies the list of response values for each of the data elements. It has subsequently been submitted for open international review with the aim of producing a globally agreed upon standard for the reporting of melanoma. After collation of all international responses, and review by the authors, the final data set will be published on the ICCR website Fig. The ICCR is currently engaged in working with a number of key international organizations to develop universally agreed upon standards for the pathology reporting of other cancers.

The efforts of respective melanoma expert committees of the Royal College of Pathologists United Kingdom , the College of American Pathologists, and the Canadian Association of Pathologists are also much appreciated. You may be trying to access this site from a secured browser on the server.

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Your Email:. Colleague's Email:. Separate multiple e-mails with a ;. Send a copy to your email. Some error has occurred while processing your request. Please try after some time. Article as PDF 1. Back to Top Article Outline. TABLE 1. TABLE 2. TABLE 3. Cutaneous melanoma in the era of molecular profiling. Cited Here PubMed CrossRef. Melanoma —a management guide for GPs. Aust Fam Physician. Melanoma pathology : important issues for clinicians involved in the multidisciplinary care of melanoma patients. Surg Oncol Clin N Am.

Standardized synoptic cancer pathology reports: so what and who cares? A population-based satisfaction survey of pathologists, surgeons, and oncologists. Arch Pathol Lab Med. The advantage of using a synoptic pathology report format for cutaneous melanoma. Protocol for the examination of specimens from patients with melanoma of the skin. College of American Pathologists, Accessed December 1, Primary cutaneous melanoma structured reporting protocol 1st edition Royal College of Pathologists of Australasia,