Metastatic Melanoma



Metastatic Melanoma


Elizabeth A. Montgomery, MD





Key Facts


Terminology



  • Spread of malignant melanoma to gastrointestinal tract



    • In contrast to rare primary melanomas that typically involve esophagus and anus


Clinical Issues



  • Most common in small bowel (about 60%)


  • Poor overall prognosis



    • With medical treatment, mean survival 6 months


    • Some patients benefit from surgical debulking of metastases (mean survival 48 months )


Microscopic Pathology



  • “Bottom heavy” infiltrate of malignant cells


  • No in situ epithelial lesion


  • Pleomorphic cells with prominent nucleoli are classic


  • Some cases can have spindle cell phenotype


  • Often requires immunolabeling to confirm


  • S100, HMB-45, melan-A, MITF often used


Top Differential Diagnoses



  • Gastrointestinal stromal tumor


  • Gastrointestinal clear cell sarcoma


  • Langerhans cell histiocytosis


  • Schwannoma


  • Benign epithelioid nerve sheath tumor


  • PEComa


  • Carcinomas and lymphomas


Diagnostic Checklist



  • Always include metastatic melanoma in differential diagnosis of tumors in the GI tract







Gross photograph shows a specimen from a small bowel resection, taken from a patient with widely metastatic melanoma with resulting small bowel obstruction. Note the striking black pigmentation.






Hematoxylin & eosin shows a melanoma metastasis to the small bowel, the most common gastrointestinal tract site for metastases. Note that the infiltrate is “bottom heavy.”


TERMINOLOGY


Definitions



  • Spread of malignant melanoma to gastrointestinal tract



    • In contrast to rare primary melanomas that typically involve esophagus and anus


CLINICAL ISSUES


Site



  • Most common in small bowel (about 60%)



    • Colorectum (about 20%)


    • Stomach (about 10%)


    • Esophagus (about 5%)


    • Cases reported in gallbladder


  • Features of melanomas that metastasize to GI tract



    • Often in lower extremity


    • Often nodular


Presentation



  • Esophageal



    • Dysphagia, retrosternal pain, weight loss


  • Gastric



    • Upper GI tract bleeding, melena


  • Small bowel



    • Ileus


  • Colorectal



    • Abdominal pain, palpable mass, anemia, weight loss


Treatment



  • Drugs



    • Some responses to specific tyrosine kinase inhibitors such as imatinib



      • Subset has KIT mutations


Prognosis



  • Poor overall



    • With medical treatment, mean survival 6 months


    • Some patients benefit from surgical debulking of metastases (mean survival 48 months)


MICROSCOPIC PATHOLOGY


Key Descriptors



  • Histologic features



    • “Bottom heavy” infiltrate of malignant cells


    • No in situ epithelial lesion


    • Pleomorphic cells with prominent nucleoli classic



      • Intranuclear cytoplasmic pseudoinclusions


      • Some cases can have spindle cell phenotype


      • Mitotically active


    • Often requires immunolabeling to confirm



      • Most lesions lack classic black pigmentation


      • S100, HMB-45, melan-A, MITF often used


      • Pitfall: Many examples are CD117(+) although most examples are CD34(−)


DIFFERENTIAL DIAGNOSIS


Gastrointestinal Stromal Tumor



  • Most common in stomach muscularis propria


  • Uniform spindled or epithelioid cells


  • CD117(+), S100(−), CD34(+)


Gastrointestinal Clear Cell Sarcoma



  • Usually in ileum as primary neoplasms


  • Packeted arrangement of uniform cells


  • Large nucleoli


  • Have gene fusions: EWS-CREB1 or EWS-ATF1


  • Often S100(+) and negative with “specific” melanocytic markers


  • Molecular testing required to diagnose some cases


Langerhans Cell Histiocytosis



  • Extremely rare



    • Occasional case reports


  • Atypical cells with nuclear grooves



  • Eosinophil-rich backdrop


  • Cells lack large nucleoli


  • S100(+), CD68(+), CD1a(+); negative for “specific” melanoma markers


Schwannoma



  • Usually in stomach


  • Prominent lymphoid cuff


  • Spindle cells with lymphoplasmacytic backdrop


  • Minimal mitotic activity


  • No prominent nucleoli


  • S100(+); negative for “specific” melanoma markers


Benign Epithelioid Nerve Sheath Tumor



  • Usually in colon


  • Based in lamina propria and muscularis mucosae


  • Small epithelioid cells with prominent intranuclear pseudoinclusions


  • Essentially amitotic


Psammomatous Melanotic Schwannoma



  • Uniform small cells with delicate small nucleoli



    • Amitotic


  • Occasional overtly melanocytic cells


  • Psammoma bodies


  • S100(+), HMB-45(+), melan-A(+)


PEComa



  • Richly vascular lesions with epithelioid spindle cells


  • Includes family of neoplasms



    • Angiomyolipoma (essentially PEComa with fat), clear cell myomelanocytic tumor, lymphangioleiomyomatosis, and clear cell “sugar” tumor of lung


  • Unified by expression of smooth muscle markers that coexpress melanocytic markers


  • S100(−)


Carcinomas and Lymphomas

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Jul 6, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Metastatic Melanoma

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