Cancers of the skin

14 Cancers of the skin




Cutaneous melanoma





Pathology


There are four histological variants of cutaneous melanoma:






Other forms of melanoma include ocular, mucosal and vulval (p. 236).


The histology of melanomas is very variable depending on the specific subtype and primary site. Many of the features assessed by histology have prognostic value (Box 14.1). In addition to these the pathologist should report the type of melanoma, greatest thickness, radial or vertical growth phase, excision margins and immunohistochemical stains. Immunohistochemical stains used in melanoma include S100 (the most frequently used but also stains benign melanocytes), HMB-45, Mitf, MART-1 and tyrosinase.







Staging


Breslow thickness, ulceration and mitotic count are most important prognostic factors of localized disease whereas Clark level is an independent prognostic factor for melanoma of <1 mm thickness (Box 14.1). Staging is by TNM AJCC system and is related to prognosis (Table 14.1). M1a includes distant skin, subcutaneous or nodal metastases with a normal LDH. M1b is lung metastases with a normal LDH and M1c is with any other metastases or with a raised LDH level.


Table 14.1 TNM staging & 5-year survival of cutaneous melanoma




















































































Staging 5-year survival (%)
Stage IA 95
T1aN0M0 ≤1 mm thickness without ulceration and mitosis <1/mm2  
Stage IB 91
T1bN0M0 ≤1 mm thickness with ulceration or mitosis ≥1/mm2  
T2aN0M0 1.01–2 mm thickness without ulceration  
Stage IIA 77–79
T2bN0M0 1.01–2 mm thickness with ulceration  
T3aN0M0 2.01–4 mm thickness without ulceration  
Stage IIB 63–67
T3bN0M0 2.01–4 mm thickness with ulceration  
T4aN0M0 >4 mm thickness without ulceration  
Stage IIC 45
T4bN0M0 >4 mm thickness with ulceration  
Stage IIIA  
T1-4aN1aM0 Micrometastasis* in 1 node 70
T1-4aN2aM0 Micrometastasis in 2–3 nodes 63
Stage IIIB  
T1-4bN1a/2aM0 50–53
T1-4aN1bM0 Macrometastasis** in 1 node 46–59
T1-4aN2bM0 Macrometastasis in 2–3 nodes 46–59
T1-4aN2cM0 in-transit metastases/satellites without nodes  
Stage IIIC 24–29
T1-4bN1b/2b/2cM0  
Any T N3M0 metastasis in >3 nodes or matted nodes or in-transit or satellites with metastatic nodes  
Stage IV  
Any T, any N, M1 distant metastasis 7–19%

*micrometastases after sentinel node biopsy; **macrometastases are clinically detectable pathologically confirmed nodes.



Management



Non-metastatic disease




Management of regional lymph node


The role of elective lymph node excision for node negative patients has being debated for several years. Although initial retrospective studies showed a survival benefit with this approach, four randomized studies failed to show any survival advantage. Debate on the role of elective node dissection has been subsumed by emergence of the sentinel node concept.


The sentinel node (SN) is the node to which the lymph initially drains from a tumour before passing to the other regional nodes. In theory the sentinel node is most likely to contain the tumour cells and if none are present in this node, it is unlikely that other lymph nodes are involved.


The risk of sentinel node metastasis depends on the thickness of lesion. A tumour less than 0.8 mm thick has 1% SN positivity, 0.8 to 1.5 mm has 8%, 1.5–4 mm thickness has 23% and more than 4 mm thickness has 36% risk. Although, sentinel node positivity is proven to have strong correlation with survival (90% 5-year survival for SN negative vs. 56% for SN positive), the role of lymph node dissection for SN positive disease is still evolving. Many agree that there is no proven overall survival benefit from the routine application of SN to patients with cutaneous melanoma. However, there is some suggestion that it may increase the disease free survival.


Patients with >4 mm thick lesions have a predicted incidence of SN positivity of 30–40%. Hence it is reasonable to offer SN in this group of patients to provide prognostic information and selection into clinical trials.


The ongoing MSLT-II trial aims to examine the benefit of complete dissection on survival by randomizing patients with SN positive melanoma to undergo either complete nodal dissection or observation.





Management of metastatic disease


Metastatic melanoma has a poor prognosis. Most patients with non-visceral metastases survive up to 18 months whereas the median survival of those with visceral involvement or an elevated serum LDH is 4–6 months. Lymph node and skin metastases in the absence of other metastases have the best prognosis (up to 18 months). Those with lung metastases in the absence of other visceral disease have an intermediate prognosis (up to 12 months median survival). Those with other visceral disease have a median survival of less than 6 months which is limited further in the presence of a high and rapidly increasing LDH. Patients with liver metastases from a primary uveal melanoma have a particularly poor prognosis usually limited to less than 3 months.


Treatment of melanoma metastases depends on the site of disease, whether or not it is localized and the overall fitness of the patient. Treatment can be with surgery, radiotherapy, systemic therapies or best supportive care.





Chemotherapy and other systemic treatments in metastatic disease


Dacarbazine is the standard intravenous chemotherapy drug for metastatic melanoma with a response rate of 10–20% and a median duration of response of 3–6 months. It is given 3–4 weekly at doses of 850–1000 mg/m2 with nausea as the main side effect. Temozolamide is an oral analogue of dacarbazine and crosses the blood–brain barrier but is more expensive and has no improvement in response rates compared with dacarbazine (Table 14.2). There is no evidence that combination chemotherapy regime is superior to single agent drugs in terms of response rates or survival.


Table 14.2 Response rates (%) for single agents in metastatic melanoma





























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Jun 18, 2016 | Posted by in ONCOLOGY | Comments Off on Cancers of the skin

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Agent % Response rate (CR + PR)
Dacarbazine 20
Temozolamide 21
Carmustine (BCNU) 18
Lomustine (CCNU) 13
Cisplatin 23
Carboplatin 16
Vinblastine 13
Paclitaxel