they may be the first manifestation of metastatic spread of an internal malignancy or herald cancer recurrence long after treatment of a primary tumor . breast cancer , colorectal cancer , and melanoma frequently metastasize to the skin in women . in men ; melanoma , lung cancer , and colorectal cancer are the most common sources of cutaneous metastases . however , such patterns may differ geographically as a study in taiwan found internal malignancies metastasize to the skin with different frequencies and at rates differing from primarily caucasian populations . an extensive literature review was conducted using pubmed from may 26 , 2011-july 16 , 2013 relating cutaneous metastases . articles chosen for reference were queried with the following prompts :  cutaneous metastases  ,  clinical presentation  ,  histological features  , and further searches included  treatment  and  management  options for  metastatic breast  ,  metastatic colorectal  ,  metastatic melanoma  ,  metastatic lung  , and  hematologic cancers  . we review the literature on clinical presentation , diagnosis , and advances in the management . cutaneous metastases may be asymptomatic or be associated with pain and tenderness [ figure 1a ] . they frequently present as a rapidly growing painless dermal or subcutaneous nodules with intact overlying epidermis [ figures 1b  d ] , but can also mimic an inflammatory dermatosis . metastases may also present as macules , infiltrated or indurated plaques , discoid lesions , tumor nodules with telangiectasias , bullous or papulosquamous lesions , scarred plaques , or pigmented tumors . while there is no single diagnostic characteristic which predominates ; a few patterns have been recognized . ( a ) gingival metastases from a primary chondrosarcoma.(b ) firm nodule at the base of the ear from a primary lung cancer . ( c ) two subcutaneous firm nodules in the clavicular fossa from metastatic lung cancer . ( d ) isolated firm nodular lesion from metastatic colon cancer metastases originating from breast cancer tend to appear in the anterior chest wall , either from direct extension of underlying tumor or by lymphatic spread [ figures 2a and 3a ] . extensive cutaneous involvement of metastatic breast cancer can simulate cellulitis ( carcinoma erysipeloides ) or a breast - plate of armor ( " en cuirasse " pattern ) . interestingly , a subset of breast cancer patients has superior prognosis , even among breast cancer patients with stage iv disease . ( a ) cellulitis - like appearance of metastatic breast cancer.(b ) plaque - like area with multiple nodules from a primary breast cancer . ( c ) massive recurrence of breast cancer on the chest wall and abdomen of the  en cuirasse  type . ( d ) breast cancer , metastatic to the thoracic spine with extension to the skin , and lceration secondary to radiation therapy ( a ) cellulitic - type appearance with multiple nodules in metastatic breast cancer of the shoulder and upper back . a cam 5.2 stain reveals perinuclear staining ( original magnification , 400).(c ) metastatic squamous cell carcinoma of the skin reveals neoplastic cells in the dermis ( cytokeratin 5/6 stain ; original magnification , 100 ) . a her2/neu stain is positive and decorates the neoplastic cells in the dermis indicating possible metastasis from breast carcinoma ( original magnification , 200 ) while most cancers present as solitary nodules , melanoma and carcinomas with an unknown primary frequently present as multiple nodules . locoregional melanocytic metastases may be explained by angiotropism , an extravascular migratory phenotype , and an important marker and prognostic factor of metastasis in melanoma . the face and scalp are most commonly affected by metastases , suggesting that blood vessels and patterns of innervation may influence the spread of metastases . these patterns can also been associated with cancers of gastric , pulmonary , prostatic , ovarian , laryngeal , palatine - tonsillar , pancreatic , colorectal , parotid , thyroid , or uterine origin and may suggest local treatments that work for melanoma may also work for other metastatic cutaneous malignancies . although metastases may be comprised of cells which are more undifferentiated than the primary tumor , careful examination usually reveals important clues . for example , melanoma is associated with pigment in at least some of the neoplastic cells in most cases . squamous cell carcinoma is associated with keratin pearl formation , and adenocarcinomas usually exhibit gland formation . thyroid cancer may exhibit colloid bodies , colon cancer may be associated with mucinous cells , and other tumors may exhibit telltale clues as to their origin . when confronted with a possible metastasis , comparison with the histologic appearance of any prior malignant neoplasms is usually one of the first steps that may help identify the source . additionally , studies have indicated the majority of metastatic cancers to the skin are adenocarcinomas . when tumors are poorly differentiated or anaplastic , screening immunohistochemical studies can be very helpful . when neoplastic cells stain with cytokeratin markers such as ae1/ae3 and cam 5.2 , a carcinoma is likely [ figure 3b ] . staining with cd45/leukocyte common antigen ( lca ) indicates that neoplastic cells are of lymphoid origin , while s-100 , melan - a , mart-1 , hmb-45 , and sox-10 decorate most melanomas . more detailed immunohistochemical studies [ table 2 ] can be performed when screening studies and clinical correlation have not been fruitful in identifying a tumor of origin . although advances in immunohistochemistry are very promising , there is still much work that needs to be done to characterize metastases . a recent letter to the editor highlights the pitfalls that can occur when differentiating primary cutaneous apocrine carcinoma from a metastasis . although cytokeratin 5/6 is associated with cutaneous apocrine carcinoma , this staining pattern has also been noted with metastatic squamous cell carcinoma [ figure 3c ] . similarly , cytokeratin 7 usually stains metastases diffusely , but is associated with only focal staining in primary adnexal carcinoma , but this pattern is not absolute . mammaglobin is of interest as it is associated with more widespread staining of metastases than primary apocrine carcinoma , but the results are still preliminary . cyclooxygenase 2 is associated with tumors of the mid - gut ( ileum and appendix ) , gut , colorectal adenocarcinoma as well as gastroesophageal adenocarcinoma . staining of adenocarcinoma of the lung and endometrioid adenocarcinoma can also occur , highlighting the fact that all immunochemical marker studies must be interpreted in the context of other findings . when an epithelial carcinoma is identified , cytokeratin 7 and 20 stains can provide important useful characterization of tumors . additional testing can include thyroid transcription factor-1 ( ttf-1 ) and other markers as needed . when clinical appearance , clinical history , and the histologic findings on biopsy are all taken into account unfortunately , there are still many cases that elude precise diagnosis regarding whether a tumor is primary or metastatic . recent reports have proposed a diagnostic algorithm for metastatic tumors of unknown primary . until better methods are developed we recommend excising metastases when surgically feasible and when this will result in a significant decrease in total tumor burden , improve quality of life , or result in increased functionality . novel treatments have had a profound effect on prolonging the survival and improving quality of life with metastatic cancer . oftentimes , treatment of the primary cancer with a successful regimen will cause cutaneous lesions to lessen . interestingly , the abscopal response represents an unusual response to radiation therapy in which radiation of a tumor causes untreated distant skin lesions to dissipate without recurrence . the pathophysiology and mechanism of the abscopal effect have not been well - defined , but one study used monoclonal antibodies to analyze infiltrating lymphocytes and suggested that the abscopal effect was caused by activated cellular immunity . the abscopal response has been reported with treatment of melanoma , merkel cell carcinoma , hematologic , and solid tumors . the study of effective local treatments for melanoma may serve as a model for other malignancies that disseminate via lymphatics and the blood stream to the skin . for melanomas , we typically excise isolated metastases with a 1 cm margin of normal skin , understanding that there are no evidence based studies looking at the utility of margins for metastatic disease . in areas of high cosmetic importance or when therapy is limited to palliation , we sometimes perform excisions with very limited margins . therapy for patients with widespread cutaneous and subcutaneous metastases of advanced melanoma that are nonresectable is limited to other types of palliative therapy . options include radiotherapy , systemic chemotherapy , polychemotherapy , isolated limb perfusion , interferon alpha injections , cryotherapy , laser ablation , or radiofrequency ablation . electrochemotherapy is a novel therapeutic option based on enhanced drug delivery into cancer cells using externally applied electrical fields that increase cell membrane permeability . using targeted electric pulses on tumor - specific areas , cytotoxicity of cisplatin increased 80 times and bleomycin 8,000 times with a large reduction in systemic side effects . a study comparing tumor nodules treated with electrochemotherapy with cisplatin versus cisplatin alone found at a 124-week follow - up , 77% of control rate of tumor nodules treated with electrochemotherapy was observed compared to 19% for those treated with cisplatin only . electrochemotherapy is well - tolerated by patients , highly effective with low doses of cisplatin or bleomycin , has a short duration of treatment sessions , insignificant side effects , and is more cost - effective than isolated limb perfusion , radiotherapy , interferon - alpha , and hyperthermia associated with radiotherapy and chemotherapy . oncogene - targeted therapy for metastatic melanoma using vemurafenib ( plx4032 ) for melanoma associated with a mutation of the braf gene v600 mutation results in complete or partial tumor regression in the majority of patients with an estimated median progression - free survival of more than 7 months . side effects include arthralgia , rash , nausea , photosensitivity , fatigue , cutaneous squamous - cell carcinoma , pruritus , and palmoplantar dysesthesia . imiquimod 5% cream has also been used successfully in the treatment of metastatic melanoma that is difficult to remove by surgery . in one report , a 58-year - old woman with a superficial spreading melanoma with a breslow thickness 0.75 mm was treated with wide local excision followed by flap reconstruction . melanoma reemerged 14 months later that was treated with wide local excision followed by split - thickness graft repair . the patient was enrolled in a melanoma peptide vaccine trial 5 months later without improvement . twenty - one months later , the patient was treated with imiquimod 5% cream and histopathologic evaluation revealed regression of the widespread cutaneous metastases after 6 months of imiquimod . any change in the skin should raise the suspicion of metastases in the correct clinical context . biopsy is mandatory in patients with a history of cancer or those with at high risk of cancer . immunohistochemical screening methods continue to improve and assist in diagnosing the primary tumors of origin . immunohistochemical findings can also help direct treatment options . with advances in novel therapies that prolong survival ,
skin metastases are rare in the routine clinical practice of dermatology , but are of major clinical significance because they usually indicate advanced disease . 
 we reviewed the literature on skin metastasis regarding recent trends in clinical presentation and diagnosis of the most common cutaneous lesions . 
 an extensive literature review was conducted using pubmed from may 26 , 2011 to july 16 , 2013 relating cutaneous metastases . 
 articles chosen for reference were queried with the following prompts :  cutaneous metastases  ,  clinical presentation  ,  histological features  , and 
 immunohistochemistry  . 
 further searches included  treatment  and  management  options for  metastatic breast  ,  metastatic colorectal  ,  metastatic melanoma  ,  metastatic lung  , and  hematologic cancers . 
 we also reviewed the literature on the current management of melanoma as a model for all cutaneous metastatic disease . 
 our own clinical findings are presented and compared to the literature . 
 additionally , we highlight the most useful immunohistochemical studies that aid in diagnoses . 
 several novel therapies and combination therapies such as electrochemotherapy , vemurafenib , and imiquimod will be discussed for palliative treatment of cancers that have been found to improve cutaneous lesions . 
 we review these notable findings and developments regarding skin metastases for the general dermatologist .