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Pathologic Assessment of Lymph Node Metastasis

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Cancer Metastasis Through the Lymphovascular System
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Abstract

The pathologic assessment and evaluation of lymph node status plays a central role in the diagnosis, staging, and management of most malignancies. The pathologic status of the lymph node plays a central role in the staging, and thus subsequent treatment of diseases, which is codified in the AJCC/UICC staging system. Lymph node metastasis may be subclinical and detected microscopically during surgical resection of a sentinel node or regional lymphadenectomy for initial therapy, or it may present clinically as the first manifestation of a metastatic malignancy. Different protocols exist for the pathologic evaluation of lymph nodes in these distinct settings. These involve systematic gross assessment, careful light microscopic evaluation, judicious and sometimes stepwise application of immunohistochemical methods, and accurate pathologic reporting. The evaluation of a lymph node metastasis in a patient with unknown primary malignancy requires knowledge of the relative frequencies of malignancies, their most common sites of presentation, and an algorithmic approach to immunohistochemical testing. Molecular analysis by gene expression profiling offers modest improvement in diagnostic accuracy, but these improvements have not yet been translated into clinical improvements.

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References

  1. Urteaga O, Pack GT. On the antiquity of melanoma. Cancer. 1966;19(5):607–10.

    Article  CAS  PubMed  Google Scholar 

  2. Gorantla VC, Kirkwood JM. State of melanoma: an historic overview of a field in transition. Hematol Oncol Clin North Am. 2014;28(3):415–35.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Cooper S. The first lines of the theory and practice of surgery. London: Longman; 1840.

    Google Scholar 

  4. Snow HM. Melanoma cancerous disease. Lancet. 1892;140:869–922.

    Article  Google Scholar 

  5. Faries MB, et al. Lymph node metastasis in melanoma: a debate on the significance of nodal metastases, conditional survival analysis and clinical trials. Clin Exp Metastasis. 2018;35(5–6):431–42.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Denoix P. Nomenclature classification des cancers. Bull Inst Nat Hyg (Paris). 1952;7:743–8.

    Google Scholar 

  7. Hutter RV. At last—worldwide agreement on the staging of cancer. Arch Surg. 1987;122(11):1235–9.

    Article  CAS  PubMed  Google Scholar 

  8. Amin MB. AJCC cancer staging manual. 8th ed. Switzerland: Springer Nature; 2017.

    Book  Google Scholar 

  9. Surgery basic science and clinical evidence. 2nd ed. Springer Nature; 2008.

    Google Scholar 

  10. Cabanas RM. An approach for the treatment of penile carcinoma. Cancer. 1977;39(2):456–66.

    Article  CAS  PubMed  Google Scholar 

  11. Morton DL, et al. Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg. 1992;127(4):392–9.

    Article  CAS  PubMed  Google Scholar 

  12. Fayne RA, et al. Evolving management of positive regional lymph nodes in melanoma: past, present and future directions. Oncol Rev. 2019;13(2):433.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Zeitoun J, Babin G, Lebrun JF. Sentinel node and breast cancer: a state-of-the-art in 2019. Gynecol Obstet Fertil Senol. 2019;47(6):522–6.

    CAS  PubMed  Google Scholar 

  14. Faries MB. Application of senitnel lymph node surgery outside of melanoma and breast cancer. Clin Exp Metastasis. 2021;

    Google Scholar 

  15. Burghgraef TA, et al. In vivo sentinel lymph node identification using fluorescent tracer imaging in colon cancer: a systematic review and meta-analysis. Crit Rev Oncol Hematol. 2021;158:103,149.

    Article  CAS  Google Scholar 

  16. Vuijk FA, et al. Fluorescent-guided surgery for sentinel lymph node detection in gastric cancer and carcinoembryonic antigen targeted fluorescent-guided surgery in colorectal and pancreatic cancer. J Surg Oncol. 2018;118(2):315–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Cancer Protocol Templates. 2021 [cited 2021; Available from: https://www.cap.org/protocols-and-guidelines/cancer-reporting-tools/cancer-protocol-templates.

  18. Narayanan R, Wilson TG. Sentinel node evaluation in prostate cancer. Clin Exp Metastasis. 2018;35(5–6):471–85.

    Article  PubMed  Google Scholar 

  19. Cotarelo CL, et al. Improved detection of sentinel lymph node metastases allows reliable intraoperative identification of patients with extended axillary lymph node involvement in early breast cancer. Clin Exp Metastasis. 2021;38(1):61–72.

    Article  CAS  PubMed  Google Scholar 

  20. Osarogiagbon RU, et al. Survival implications of variation in the thoroughness of pathologic lymph node examination in American College of Surgeons Oncology Group Z0030 (Alliance). Ann Thorac Surg. 2016;102(2):363–9.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Gleisner AL, et al. Nodal status, number of lymph nodes examined, and lymph node ratio: what defines prognosis after resection of colon adenocarcinoma? J Am Coll Surg. 2013;217(6):1090–100.

    Article  PubMed  Google Scholar 

  22. Wright JL, Lin DW, Porter MP. The association between extent of lymphadenectomy and survival among patients with lymph node metastases undergoing radical cystectomy. Cancer. 2008;112(11):2401–8.

    Article  PubMed  Google Scholar 

  23. Chan JK, et al. Metastatic gynecologic malignancies: advances in treatment and management. Clin Exp Metastasis. 2018;35(5–6):521–33.

    Article  PubMed  Google Scholar 

  24. Mansour J, et al. Prognostic value of lymph node ratio in metastatic papillary thyroid carcinoma. J Laryngol Otol. 2018;132(1):8–13.

    Article  CAS  PubMed  Google Scholar 

  25. Mozzillo N, et al. Sentinel node biopsy in thin and thick melanoma. Ann Surg Oncol. 2013;20(8):2780–6.

    Article  PubMed  Google Scholar 

  26. Leong SP, et al. Clinical patterns of metastasis. Cancer Metastasis Rev. 2006;25(2):221–32.

    Article  PubMed  Google Scholar 

  27. Hemminki K, et al. Site-specific cancer deaths in cancer of unknown primary diagnosed with lymph node metastasis may reveal hidden primaries. Int J Cancer. 2013;132(4):944–50.

    Article  CAS  PubMed  Google Scholar 

  28. Kawaguchi T. Pathological features of lymph node metastasis. 2 from morphological aspects. Nihon Geka Gakkai Zasshi. 2001;102(6):440–4.

    CAS  PubMed  Google Scholar 

  29. Zhou H, Lei PJ, Padera TP. Progression of metastasis through lymphatic system. Cell. 2021;10(3)

    Google Scholar 

  30. Cote RJ, et al. Role of immunohistochemical detection of lymph-node metastases in management of breast cancer. International Breast Cancer Study Group. Lancet. 1999;354(9182):896–900.

    Article  CAS  PubMed  Google Scholar 

  31. Messina JL, et al. Pathologic examination of the sentinel lymph node in malignant melanoma. Am J Surg Pathol. 1999;23(6):686–90.

    Article  CAS  PubMed  Google Scholar 

  32. Euscher ED, et al. Ultrastaging improves detection of metastases in sentinel lymph nodes of uterine cervix squamous cell carcinoma. Am J Surg Pathol. 2008;32(9):1336–43.

    Article  PubMed  Google Scholar 

  33. Su LD, et al. Immunostaining for cytokeratin 20 improves detection of micrometastatic Merkel cell carcinoma in sentinel lymph nodes. J Am Acad Dermatol. 2002;46(5):661–6.

    Article  PubMed  Google Scholar 

  34. Abdel-Halim CN, et al. Histopathological definitions of extranodal extension: a systematic review. Head Neck Pathol. 2021;15(2):599–607.

    Article  PubMed  Google Scholar 

  35. Dekker J, Duncan LM. Lack of standards for the detection of melanoma in sentinel lymph nodes: a survey and recommendations. Arch Pathol Lab Med. 2013;137(11):1603–9.

    Article  PubMed  Google Scholar 

  36. Cole CM, Ferringer T. Histopathologic evaluation of the sentinel lymph node for malignant melanoma: the unstandardized process. Am J Dermatopathol. 2014;36(1):80–7.

    Article  PubMed  Google Scholar 

  37. Bautista NC, Cohen S, Anders KH. Benign melanocytic nevus cells in axillary lymph nodes. A prospective incidence and immunohistochemical study with literature review. Am J Clin Pathol. 1994;102(1):102–8.

    Article  CAS  PubMed  Google Scholar 

  38. Carson KF, et al. Nodal nevi and cutaneous melanomas. Am J Surg Pathol. 1996;20(7):834–40.

    Article  CAS  PubMed  Google Scholar 

  39. Biddle DA, et al. Intraparenchymal nevus cell aggregates in lymph nodes: a possible diagnostic pitfall with malignant melanoma and carcinoma. Am J Surg Pathol. 2003;27(5):673–81.

    Article  PubMed  Google Scholar 

  40. Koh SS, Cassarino DS. Immunohistochemical expression of p16 in melanocytic lesions: an updated review and meta-analysis. Arch Pathol Lab Med. 2018;142(7):815–28.

    Article  CAS  PubMed  Google Scholar 

  41. Lezcano C, et al. Immunohistochemistry for PRAME in the distinction of nodal nevi from metastatic melanoma. Am J Surg Pathol. 2020;44(4):503–8.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Kamposioras K, et al. Malignant melanoma of unknown primary site. To make the long story short. A systematic review of the literature. Crit Rev Oncol Hematol. 2011;78(2):112–26.

    Article  CAS  PubMed  Google Scholar 

  43. Lester S et al. Protocol for the examination of specimens from patients with invasive carcinoma of the breast; December 2013.

    Google Scholar 

  44. Lyman GH, et al. Sentinel lymph node biopsy for patients with early-stage breast cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2014;32(13):1365–83.

    Article  PubMed  Google Scholar 

  45. Wiatrek R, Kruper L. Sentinel lymph node biopsy indications and controversies in breast cancer. Maturitas. 2011;69(1):7–10.

    Article  PubMed  Google Scholar 

  46. Siegel RL, et al. Cancer statistics, 2021. CA Cancer J Clin. 2021;71(1):7–33.

    Article  PubMed  Google Scholar 

  47. Buttar A, et al. Cancers of unknown primary. In: Pieters R, editor. Cancer concepts: a guidebook for the non-oncologist. University of Massachusetts Medical School; 2015.

    Google Scholar 

  48. Hemminki K, et al. Survival in cancer of unknown primary site: population-based analysis by site and histology. Ann Oncol. 2012;23(7):1854–63.

    Article  CAS  PubMed  Google Scholar 

  49. Losa F, et al. 2018 consensus statement by the Spanish Society of Pathology and the Spanish Society of Medical Oncology on the diagnosis and treatment of cancer of unknown primary. Clin Transl Oncol. 2018;20(11):1361–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Chorost MI, et al. Unknown primary. J Surg Oncol. 2004;87(4):191–203.

    Article  PubMed  Google Scholar 

  51. Hainsworth JD, Fizazi K. Treatment for patients with unknown primary cancer and favorable prognostic factors. Semin Oncol. 2009;36(1):44–51.

    Article  CAS  PubMed  Google Scholar 

  52. Jereczek-Fossa BA, Jassem J, Orecchia R. Cervical lymph node metastases of squamous cell carcinoma from an unknown primary. Cancer Treat Rev. 2004;30(2):153–64.

    Article  PubMed  Google Scholar 

  53. Kandalaft PL, Gown AM. Practical applications in immunohistochemistry: carcinomas of unknown primary site. Arch Pathol Lab Med. 2016;140(6):508–23.

    Article  CAS  PubMed  Google Scholar 

  54. Pentheroudakis G, Golfinopoulos V, Pavlidis N. Switching benchmarks in cancer of unknown primary: from autopsy to microarray. Eur J Cancer. 2007;43(14):2026–36.

    Article  PubMed  Google Scholar 

  55. Binder C, et al. Cancer of unknown primary-epidemiological trends and relevance of comprehensive genomic profiling. Cancer Med. 2018;7(9):4814–24.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Ettinger DS, et al. NCCN Clinical Practice Guidelines Occult primary. J Natl Compr Cancer Netw. 2011;9(12):1358–95.

    Article  Google Scholar 

  57. Bochtler T, Löffler H, Krämer A. Diagnosis and management of metastatic neoplasms with unknown primary. Semin Diagn Pathol. 2018;35(3):199–206.

    Article  PubMed  Google Scholar 

  58. Bellizzi AM. An algorithmic Immunohistochemical approach to define tumor type and assign site of origin. Adv Anat Pathol. 2020;27(3):114–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Houston KA, et al. Patterns in lung cancer incidence rates and trends by histologic type in the United States, 2004-2009. Lung Cancer. 2014;86(1):22–8.

    Article  PubMed  Google Scholar 

  60. Banerjee SS, Harris M. Morphological and immunophenotypic variations in malignant melanoma. Histopathology. 2000;36(5):387–402.

    Article  CAS  PubMed  Google Scholar 

  61. Pavlidis N. Cancer of unknown primary: biological and clinical characteristics. Ann Oncol. 2003;14(Suppl 3)):11–8.

    Article  Google Scholar 

  62. Lee MS, Sanoff HK. Cancer of unknown primary. BMJ. 2020;371:m4050.

    Article  PubMed  Google Scholar 

  63. Weiss LM, et al. Blinded comparator study of immunohistochemical analysis versus a 92-gene cancer classifier in the diagnosis of the primary site in metastatic tumors. J Mol Diagn. 2013;15(2):263–9.

    Article  CAS  PubMed  Google Scholar 

  64. Handorf CR, et al. A multicenter study directly comparing the diagnostic accuracy of gene expression profiling and immunohistochemistry for primary site identification in metastatic tumors. Am J Surg Pathol. 2013;37(7):1067–75.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Hainsworth JD, et al. Molecular gene expression profiling to predict the tissue of origin and direct site-specific therapy in patients with carcinoma of unknown primary site: a prospective trial of the Sarah Cannon research institute. J Clin Oncol. 2013;31(2):217–23.

    Article  CAS  PubMed  Google Scholar 

  66. Hayashi H, et al. Randomized phase II trial comparing site-specific treatment based on gene expression profiling with carboplatin and paclitaxel for patients with cancer of unknown primary site. J Clin Oncol. 2019;37(7):570–9.

    Article  CAS  PubMed  Google Scholar 

  67. Pavlidis N, Pentheroudakis G. Cancer of unknown primary site. Lancet. 2012;379(9824):1428–35.

    Article  PubMed  Google Scholar 

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Correspondence to Jane L. Messina .

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Isom, J., Messina, J.L. (2022). Pathologic Assessment of Lymph Node Metastasis. In: Leong, S.P., Nathanson, S.D., Zager, J.S. (eds) Cancer Metastasis Through the Lymphovascular System. Springer, Cham. https://doi.org/10.1007/978-3-030-93084-4_6

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