eMedicine Specialties > Dermatology > Malignant Neoplasms

Metastatic Carcinoma of the Skin: Differential Diagnoses & Workup

Author: Thomas N Helm, MD, Clinical Associate Professor, Departments of Dermatology and Pathology, State University of New York at Buffalo; Director, Buffalo Medical Group Dermatopathology Laboratory
Coauthor(s): Thomas C Lee, MD, Intern, Department of Internal Medicine, New York University School of Medicine
Contributor Information and Disclosures

Updated: Aug 14, 2008

Differential Diagnoses

Branchial Cleft Cyst
Cellulitis
Dermatofibroma
Herpes Zoster
Pyogenic Granuloma (Lobular Capillary Hemangioma)

Workup

Laboratory Studies

  • The diagnosis of metastatic carcinoma hinges on histopathologic evaluation of involved skin. Tumors may show characteristics of the underlying tumor, or they may have a more anaplastic appearance. In the situation of an anaplastic tumor, immunohistochemical marker studies and ultrastructural examination may help delineate the tissue of origin.
  • Carcinoma immunophenotypes, with the location and antibody positivity/negativity, are as follows, with (+) indicating "always positive" and (-) indicating "negative but with rare exceptions." Additionally, CK is isoenzymes of creative kinase, TTF is thyroid transcription factor, Ber-EP4 is antihuman epithelial antigen, WT-1 is Wilms tumor protein, CEA is carcinoembryonic antigen, ER is estrogen receptor, and CA is cancer antigen. 
    • Breast - CK7 (+), CAM 5.2 (+), vimentin (-), TTF-1 (-), Ber-EP4 (+), WT-1 (-), DPC4 (-)
    • Lung adenocarcinoma - CK7 (+), CAM 5.2 (+), CEA (+), Ber-EP4 (+), WT-1 (-), DPC4 (-)
    • Colorectal - CK20 (+), CAM 5.2 (+), CK17 (-), CK19 (+), CEA (+), TTF-1 (-), Ber-EP4 (+), S100 (-), WT-1 (-), DPC4 (-)
    • Gastric - CAM 5.2 (+), vimentin (-), TTF-1 (-), ER (-), Ber-EP4 (+), WT-1 (-), DPC4 (-)
    • Prostate - CK7 (-), CK20 (-), CAM 5.2 (+), CD5/6 (-), CK17 (-), CEA (-), vimentin (-), TTF-1 (-), ER (-), Ber-EP4 (+), S100 (-), WT-1 (-), DPC4 (-)
    • Pancreas - CK7 (+), CAM 5.2 (+), vimentin (-), TTF-1 (-), ER (-), Ber-EP4 (+), S100 (-), WT-1 (-), DPC 4 (+)
    • Renal - CK7 (-), CK20 (-), CAM 5.2 (+), CEA (-), TTF-1 (-), CA125 (-), ER (-), CD10 (+), WT-1 (-), DPC4 (-)
    • Neuroendocrine - CK20 (-), CK5/6 (-), CA125 (-), ER (-), Ber-EP4 (-), WT-1 (-), DPC4 (-)
    • Squamous cell carcinoma - CK7 (-), CK20 (-), CK5/6 (+), CK17 (+), TTF-1 (-), CA19.9 (-), CA125 (-), ER (-), Ber-EP4 (-), CD10 (-), S100 (-), WT-1 (-), DPC4 (-)
    • Merkel cell carcinoma - CK7 (-), CK20 (+), CK5/6 (-), CEA (-), CEA (-), CA125 (-), Ber-EP4 (+), CD10 (-), S100 (-), WT-1 (-), DPC4 (-)
  • Immunohistochemical screening studies can be used in cases in which no clues point to a particular type of underlying cancer (see Media File 10).
  • Screening immunophenotypes for undifferentiated neoplasms are as follows:
    • Carcinoma - AE1/AE3 (positive), vimentin (negative), LCA (leukocyte common antigen) (negative), S-100 (negative)
    • Sarcoma - AE1/AE3 (negative), vimentin (positive), LCA (negative), S-100 (negative)
    • Lymphoma - AE1/AE3 (negative), vimentin (negative), LCA (positive), S-100 (negative)
    • Melanoma: AE1/AE3 (negative), vimentin (positive), LCA (negative), S-100 (positive)

Imaging Studies

  • Use MRI, CT, and ultrasonography in select cases if the biopsy sample is impartial or if performing a biopsy is dangerous because of proximity to vital organs.
  • Exciting recent developments include serologic testing for immune complexes. The serum TA90 immune complex assay developed at M.D. Anderson Cancer Center and licensed through Quest Diagnostics can predict the likelihood of melanoma recurrence with 70% sensitivity and 85% specificity.2 Similar studies are being developed for other types of cancer to help identify patients at high risk for metastasis.

Procedures

  • A biopsy of the skin helps in confirming a diagnosis of tumor. The pattern noted and the microscopic appearance often suggest the likely tissue of origin.

Histologic Findings

The initial diagnosis can be made by examining frozen sections, but the final diagnosis should be reserved until permanent sections are included. Generally, the histologic features of the metastases are similar to the primary tumor, although metastases may be more anaplastic and exhibit less differentiation. Cases, such as renal cell carcinoma, can be identified through characteristic histologic findings, but, usually, metastases are only classified broadly as adenocarcinoma, squamous cell carcinoma, or undifferentiated carcinoma (see Media Files 3-8).

Certain attributes distinguish metastases from the primary site. Some features include neoplastic cells in lymphatic and blood vessels, a large portion of neoplasm in the deep reticular dermis, and subcutaneous fat and neoplastic cells lined up between collagen bundles. Metastatic tumors are usually round, discrete tumor lobules in the dermis, with a Grenz zone, and are usually unassociated with the epidermis. Physical patterns vary among different carcinomas. Fibrosis and inflammation may be present. Vascular involvement is rare. Sometimes, unusual patterns can be identified. Some primary melanomas may arise in the dermis and simulate a metastasis.3 On the other hand, some metastases may be epidermotropic and simulate a primary epidermal tumor.4

Paget disease typically has a distinct clinical and histologic presentation, with involvement of the nipple or the areola. Symptoms may include an eczematous patch, with intense scaling, pain, and bleeding in later stages. Paget disease may be a sign of underlying breast, genitourinary, or colon cancer, or it may be a primary neoplasm of indeterminate glands in the skin. In extraordinary situations, lesions may be pigmented and epidermotropic and simulate melanoma. Also see Paget Disease.

More on Metastatic Carcinoma of the Skin

Overview: Metastatic Carcinoma of the Skin
Differential Diagnoses & Workup: Metastatic Carcinoma of the Skin
Treatment & Medication: Metastatic Carcinoma of the Skin
Follow-up: Metastatic Carcinoma of the Skin
Multimedia: Metastatic Carcinoma of the Skin
References
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References

  1. Krathen RA, Orengo IF, Rosen T. Cutaneous metastasis: a meta-analysis of data. South Med J. Feb 2003;96(2):164-7. [Medline].

  2. Chung MH, Gupta RK, Essner R, Ye W, Yee R, Morton DL. Serum TA90 immune complex assay can predict outcome after resection of thick (> or =4 mm) primary melanoma and sentinel lymphadenectomy. Ann Surg Oncol. Mar 2002;9(2):120-6. [Medline].

  3. Cassarino DS, Cabral ES, Kartha RV, Swetter SM. Primary dermal melanoma: distinct immunohistochemical findings and clinical outcome compared with nodular and metastatic melanoma. Archives of Dermatology. January 2008;144:49-56. [Medline].

  4. Requena L, Sangueza M, Sangueza O, Kutzner H. Pigmented mammary Paget disease and pigmented epidermotropic metastases from breast carcinoma. American Journal of Dermatopathology. June 2002;24:189-98. [Medline].

  5. Hill S, Thomas JM. Use of the carbon dioxide laser to manage cutaneous metastases from malignant melanoma. Br J Surg. Apr 1996;83(4):509-12. [Medline].

  6. Lingam MK, McKay AJ. Carbon dioxide laser ablation as an alternative treatment for cutaneous metastases from malignant melanoma. Br J Surg. Oct 1995;82(10):1346-8. [Medline].

  7. Kubota Y, Mir LM, Nakada T, Sasagawa I, Suzuki H, Aoyama N. Successful treatment of metastatic skin lesions with electrochemotherapy. J Urol. Oct 1998;160(4):1426. [Medline].

  8. Brownstein MH, Helwig EB. Metastatic tumors of the skin. Cancer. May 1972;29(5):1298-307. [Medline].

  9. Healey PM, Malott K, Chalet MD. Cancers metastatic to the skin. In: Friedman RJ, Rigel DS, Harris MN, Baker D. Cancer of the Skin. Philadelphia, Pa: WB Saunders; 1991:347-63.

  10. Lookingbill DP, Helm KF. Metastatic tumors. In: Demis J. Clinical Dermatology. Philadelphia, Pa: Lippincott-Raven; 1997:1-7.

  11. Resnik KS, DiLeonardo M, Gibbons G. Clinically occult cutaneous metastases. J Am Acad Dermatol. Dec 2006;55(6):1044-7. [Medline].

  12. Sahin S, Hindioglu U, Benekli M, Sivri B, Sökmensüer C, Sungur A. Peculiar inflammatory cutaneous metastasis from stomach adenocarcinoma. Br J Dermatol. Apr 1997;136(4):650-2. [Medline].

  13. Schwartz RA. Metastatic cancer of the skin. In: Skin Cancer Recognition and Management. New York, NY: Springer-Verlag; 1998:185-93.

  14. Spencer PS, Helm TN. Skin metastases in cancer patients. Cutis. Feb 1987;39(2):119-21. [Medline].

  15. Steck WD, Helwig EB. Tumors of the umbilicus. Cancer. Jul 1965;18:907-15. [Medline].

  16. Strohl RA. Cutaneous manifestations of malignant disease. Dermatol Nurs. Feb 1998;10(1):23-5. [Medline].

  17. Tschen EH, Apisarnthanarax P. Inflammatory metastatic carcinoma of the breast. Arch Dermatol. Feb 1981;117(2):120-1. [Medline].

  18. Zalla MJ, Roenigk RK. Metastatic carcinoma. In: Maloney M, Helm KF. Surgical Dermatopathology. Malden, Mass: Blackwell; 1999:389-436.

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Further Reading

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Keywords

skin cancer, cancer metastasis, carcinoma metastasis, cutaneous metastases, cutaneous metastasis, skin carcinoma, skin metastasis, skin metastases

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Contributor Information and Disclosures

Author

Thomas N Helm, MD, Clinical Associate Professor, Departments of Dermatology and Pathology, State University of New York at Buffalo; Director, Buffalo Medical Group Dermatopathology Laboratory
Thomas N Helm, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Society for Dermatologic Surgery, and American Society of Dermatopathology
Disclosure: Nothing to disclose.

Coauthor(s)

Thomas C Lee, MD, Intern, Department of Internal Medicine, New York University School of Medicine
Disclosure: Nothing to disclose.

Medical Editor

Robert A Schwartz, MD, MPH, Professor and Head of Dermatology, Professor of Medicine, Professor of Pediatrics, Professor of Pathology, Professor of Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi
Disclosure: Nothing to disclose.

Pharmacy Editor

Michael J Wells, MD, Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center
Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Warren R Heymann, MD, Head, Division of Dermatology, Professor, Department of Internal Medicine, University of Medicine and Dentistry of New Jersey
Warren R Heymann, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

CME Editor

Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University
Catherine Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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