Synchronous bilateral axillary sentinel lymph node metastases in a patient with truncal melanoma

Abstract

Sentinel lymph node (SLN) biopsy is an integral step of melanoma staging and is considered a strong prognostic indicator for long-term survival. Predicting lymphatic drainage of primary cutaneous lesions has been of academic interest since the late 19th century when Sappey hypothesized that drainage does not cross the sagittal midline.1Sappey M.P.C. Anatomie, physiologie, pathologie des vaisseaux lymphatiques considérés chez l’homme et les vertébrés. De Lahaye Publishing, 1874Google Scholar Several studies have since refuted Sappey’s work by showing cutaneous malignancies with multiple lymphatic basin drainage (MLBD) patterns, some crossing the midline.2McHugh J.B. Su L. Griffith K.A. et al.Significance of multiple lymphatic basin drainage in truncal melanoma patients undergoing sentinel lymph node biopsy.Ann Surg Oncol. 2006; 13: 1216-1223https://doi.org/10.1245/s10434-006-9014-zCrossref PubMed Scopus (32) Google Scholar, 3Ribero S. Osella Abate S. Pasquali S. et al.Multiple lymph node basin drainage in trunk melanoma is not associated with survival of sentinel lymph node-positive patients.Dermatology. 2017; 233: 205-211https://doi.org/10.1159/000477457Crossref PubMed Scopus (4) Google Scholar, 4Jacobs I.A. Chang C.K. Salti G.I. Significance of dual-basin drainage in patients with truncal melanoma undergoing sentinel lymph node biopsy.J Am Acad Dermatol. 2003; 49: 615-619https://doi.org/10.1067/S0190-9622(03)01838-3Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar, 5Jimenez R.E. Panageas K. Busam K.J. Brady M.S. Prognostic implications of multiple lymphatic basin drainage in patients with truncal melanoma.J Clin Oncol. 2005; 23: 518-524https://doi.org/10.1200/JCO.2005.00.075Crossref PubMed Scopus (37) Google Scholar, 6Porter G.A. I R.M. Berman R.S. Lee J.E. Mansfield P.F. Gershenwald J.E. Significance of multiple nodal basin drainage in truncal melanoma patients undergoing sentinel lymph node biopsy.Ann Surg Oncol. 2000; 7: 256-261https://doi.org/10.1007/s10434-000-0256-xCrossref PubMed Scopus (79) Google Scholar, 7Dale P.S. Foshag L.J. Wanek L.A. Morton D.L. Metastasis of primary melanoma to two separate lymph node basins: Prognostic significance.Ann Surg Oncol. 1997; 4: 13-18https://doi.org/10.1007/BF02316805Crossref PubMed Google Scholar, 8Howard J.H. Ozao-Choy J.J. Hiles J.M. Sim M.S. Faries M.B. Prognostic value of multiple draining lymph node basins in melanoma: A matched-pair analysis based on the John Wayne Cancer Institute Experience.Front Oncol. 2017; 7: 172https://doi.org/10.3389/fonc.2017.00172Crossref PubMed Scopus (6) Google Scholar, 9Melstrom L.G. Taylor E. Kuk D. et al.International multi-institutional management and outcome of melanoma patients with positive sentinel lymph nodes in more than one nodal basin.Ann Surg Oncol. 2014; 21: 4324-4329https://doi.org/10.1245/s10434-014-3845-9Crossref PubMed Scopus (10) Google Scholar Although MLBD is commonly seen in primary truncal melanomas, the occurrence of SLN metastasis in multiple lymphatic basins is not common. We report a case of synchronous positive bilateral axillary SLN metastasis in a patient with primary cutaneous melanoma on the posterior trunk and review what is known about SLNs in melanoma patients with MLBD. A 33-year-old man with prior tanning bed use presented with a pigmented lesion on his midthoracic back that had increased in size over the past 2 years. He had no significant past medical or surgical history and denied a family history of skin cancer. The patient had a Fitzpatrick skin phototype II with a 1 cm oval black papule with well-demarcated borders located slightly to the left of the midline back at the T2 level. A large tattoo with black, red, and blue ink was present on the left upper back adjacent to the black papule. This was the patient’s only tattoo. The remainder of his skin examination was unremarkable with approximately 20 small banal nevi scattered throughout his trunk and extremities. Histopathology of a shave skin biopsy revealed nodular melanoma with cytological atypia, lack of maturation, confluent and pagetoid growth within the epidermis, and rete bridging. The atypical melanocytes stained positive for SOX10 and Melan-A. The lesion was diagnosed as a stage pT2a nonulcerated melanoma with a Breslow thickness of 1.4 mm. Via intraoperative gamma probe and blue dye injections, SLNs were identified in the right and left axillae. On gross examination, the right axillary SLN appeared normal and the left axillary SLN was grossly pigmented. On histopathology, the right axillary SLN showed a microscopic focus of atypical subcapsular melanocytes with irregular nuclear membranes, pleomorphism, and retained melanin pigment that stained positive for Melan-A and S100 (Fig 1). The left axillary SLN showed intensely chromatic tattoo pigment-laden sinus histiocytes with a microscopic focus of atypical melanocytes with nuclear enlargement, pleomorphism, and prominent nucleoli that stained positive for Melan-A and S100 (Fig 2). Brain magnetic resonance imaging and total-body positron emission tomography scan showed no signs of distant metastasis. The patient received a final diagnosis of stage IIIA melanoma (pT2a pN2a M0).Fig 2Left axillary sentinel lymph node with tattoo pigment and focus of melanoma. A, Melan-A immunohistochemistry; original magnifications: ×100 and ×400. B, Hematoxylin and eosin stain; original magnification: ×400.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Since the patient only had micrometastatic lymph node disease, completion lymph node dissection was not performed. Bilateral axillary ultrasound surveillance was performed every 4 months. The patient completed 12 cycles of adjuvant nivolumab without complications. At the time of this case report (32 months after diagnosis), the patient had no evidence of disease. With the advent of preoperative lymphoscintigraphy, it is increasingly being recognized that patients exhibit unique lymphatic drainage pathways that cross Sappey’s lines.2McHugh J.B. Su L. Griffith K.A. et al.Significance of multiple lymphatic basin drainage in truncal melanoma patients undergoing sentinel lymph node biopsy.Ann Surg Oncol. 2006; 13: 1216-1223https://doi.org/10.1245/s10434-006-9014-zCrossref PubMed Scopus (32) Google Scholar MLBD is a well-recognized phenomenon among patients undergoing SLN biopsy (Table I), particularly in primary truncal melanomas, with an incidence ranging from 11% to 35%.2McHugh J.B. Su L. Griffith K.A. et al.Significance of multiple lymphatic basin drainage in truncal melanoma patients undergoing sentinel lymph node biopsy.Ann Surg Oncol. 2006; 13: 1216-1223https://doi.org/10.1245/s10434-006-9014-zCrossref PubMed Scopus (32) Google Scholar, 3Ribero S. Osella Abate S. Pasquali S. et al.Multiple lymph node basin drainage in trunk melanoma is not associated with survival of sentinel lymph node-positive patients.Dermatology. 2017; 233: 205-211https://doi.org/10.1159/000477457Crossref PubMed Scopus (4) Google Scholar, 4Jacobs I.A. Chang C.K. Salti G.I. Significance of dual-basin drainage in patients with truncal melanoma undergoing sentinel lymph node biopsy.J Am Acad Dermatol. 2003; 49: 615-619https://doi.org/10.1067/S0190-9622(03)01838-3Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar, 5Jimenez R.E. Panageas K. Busam K.J. Brady M.S. Prognostic implications of multiple lymphatic basin drainage in patients with truncal melanoma.J Clin Oncol. 2005; 23: 518-524https://doi.org/10.1200/JCO.2005.00.075Crossref PubMed Scopus (37) Google Scholar, 6Porter G.A. I R.M. Berman R.S. Lee J.E. Mansfield P.F. Gershenwald J.E. Significance of multiple nodal basin drainage in truncal melanoma patients undergoing sentinel lymph node biopsy.Ann Surg Oncol. 2000; 7: 256-261https://doi.org/10.1007/s10434-000-0256-xCrossref PubMed Scopus (79) Google Scholar, 7Dale P.S. Foshag L.J. Wanek L.A. Morton D.L. Metastasis of primary melanoma to two separate lymph node basins: Prognostic significance.Ann Surg Oncol. 1997; 4: 13-18https://doi.org/10.1007/BF02316805Crossref PubMed Google Scholar Axillary drainage is found in over 90% of truncal cases having MLBD, with 57% to 82% showing bilateral axillary drainage.3Ribero S. Osella Abate S. Pasquali S. et al.Multiple lymph node basin drainage in trunk melanoma is not associated with survival of sentinel lymph node-positive patients.Dermatology. 2017; 233: 205-211https://doi.org/10.1159/000477457Crossref PubMed Scopus (4) Google Scholar,4Jacobs I.A. Chang C.K. Salti G.I. Significance of dual-basin drainage in patients with truncal melanoma undergoing sentinel lymph node biopsy.J Am Acad Dermatol. 2003; 49: 615-619https://doi.org/10.1067/S0190-9622(03)01838-3Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar There is conflicting data as to whether MLBD impacts SLN positivity and disease prognosis. Some studies identified increased rates of SLN positivity in patients with MLBD, whereas others failed to detect an association (Table I).2McHugh J.B. Su L. Griffith K.A. et al.Significance of multiple lymphatic basin drainage in truncal melanoma patients undergoing sentinel lymph node biopsy.Ann Surg Oncol. 2006; 13: 1216-1223https://doi.org/10.1245/s10434-006-9014-zCrossref PubMed Scopus (32) Google Scholar, 3Ribero S. Osella Abate S. Pasquali S. et al.Multiple lymph node basin drainage in trunk melanoma is not associated with survival of sentinel lymph node-positive patients.Dermatology. 2017; 233: 205-211https://doi.org/10.1159/000477457Crossref PubMed Scopus (4) Google Scholar, 4Jacobs I.A. Chang C.K. Salti G.I. Significance of dual-basin drainage in patients with truncal melanoma undergoing sentinel lymph node biopsy.J Am Acad Dermatol. 2003; 49: 615-619https://doi.org/10.1067/S0190-9622(03)01838-3Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar, 5Jimenez R.E. Panageas K. Busam K.J. Brady M.S. Prognostic implications of multiple lymphatic basin drainage in patients with truncal melanoma.J Clin Oncol. 2005; 23: 518-524https://doi.org/10.1200/JCO.2005.00.075Crossref PubMed Scopus (37) Google Scholar, 6Porter G.A. I R.M. Berman R.S. Lee J.E. Mansfield P.F. Gershenwald J.E. Significance of multiple nodal basin drainage in truncal melanoma patients undergoing sentinel lymph node biopsy.Ann Surg Oncol. 2000; 7: 256-261https://doi.org/10.1007/s10434-000-0256-xCrossref PubMed Scopus (79) Google Scholar,8Howard J.H. Ozao-Choy J.J. Hiles J.M. Sim M.S. Faries M.B. Prognostic value of multiple draining lymph node basins in melanoma: A matched-pair analysis based on the John Wayne Cancer Institute Experience.Front Oncol. 2017; 7: 172https://doi.org/10.3389/fonc.2017.00172Crossref PubMed Scopus (6) Google Scholar MLBD was associated with decreased survival in only 1 of 4 studies (Table I).2McHugh J.B. Su L. Griffith K.A. et al.Significance of multiple lymphatic basin drainage in truncal melanoma patients undergoing sentinel lymph node biopsy.Ann Surg Oncol. 2006; 13: 1216-1223https://doi.org/10.1245/s10434-006-9014-zCrossref PubMed Scopus (32) Google Scholar,3Ribero S. Osella Abate S. Pasquali S. et al.Multiple lymph node basin drainage in trunk melanoma is not associated with survival of sentinel lymph node-positive patients.Dermatology. 2017; 233: 205-211https://doi.org/10.1159/000477457Crossref PubMed Scopus (4) Google Scholar,5Jimenez R.E. Panageas K. Busam K.J. Brady M.S. Prognostic implications of multiple lymphatic basin drainage in patients with truncal melanoma.J Clin Oncol. 2005; 23: 518-524https://doi.org/10.1200/JCO.2005.00.075Crossref PubMed Scopus (37) Google Scholar,8Howard J.H. Ozao-Choy J.J. Hiles J.M. Sim M.S. Faries M.B. Prognostic value of multiple draining lymph node basins in melanoma: A matched-pair analysis based on the John Wayne Cancer Institute Experience.Front Oncol. 2017; 7: 172https://doi.org/10.3389/fonc.2017.00172Crossref PubMed Scopus (6) Google ScholarTable 1Studies evaluating multiple lymphatic drainage basins, sentinel lymph node positivity, and prognostic indicators in patients with melanomaStudy, yearInstitutionNMLBD, %% MLBD w/ primary truncal lesion+SLN in >/= 2 basins, %MLBD a/w SLN positivity, other factors a/w SLN positivityMLBD a/w prognosisFactors a/w worse prognosisDale, 19977Dale P.S. Foshag L.J. Wanek L.A. Morton D.L. Metastasis of primary melanoma to two separate lymph node basins: Prognostic significance.Ann Surg Oncol. 1997; 4: 13-18https://doi.org/10.1007/BF02316805Crossref PubMed Google ScholarJWCI360311 (406/3603)80 (324/406)3 (120/3603)N/AN/A-Pos SLN in MLBD associated with decreased 1-, 3-, 5-year survival, decreased median survivalPorter, 20006Porter G.A. I R.M. Berman R.S. Lee J.E. Mansfield P.F. Gershenwald J.E. Significance of multiple nodal basin drainage in truncal melanoma patients undergoing sentinel lymph node biopsy.Ann Surg Oncol. 2000; 7: 256-261https://doi.org/10.1007/s10434-000-0256-xCrossref PubMed Scopus (79) Google ScholarMDACC28131 (86/281)100‡These studies only evaluated primary truncal melanomas.3 (8/281)Yes-Tumor thickness-UlcerationN/AN/AJacobs, 20034Jacobs I.A. Chang C.K. Salti G.I. Significance of dual-basin drainage in patients with truncal melanoma undergoing sentinel lymph node biopsy.J Am Acad Dermatol. 2003; 49: 615-619https://doi.org/10.1067/S0190-9622(03)01838-3Abstract Full Text Full Text PDF PubMed Scopus (22) Google ScholarUIC12232 (39/122)100‡These studies only evaluated primary truncal melanomas.3 (4/122)No-Tumor thickness-Clark levelN/AN/AJimenez, 20055Jimenez R.E. Panageas K. Busam K.J. Brady M.S. Prognostic implications of multiple lymphatic basin drainage in patients with truncal melanoma.J Clin Oncol. 2005; 23: 518-524https://doi.org/10.1200/JCO.2005.00.075Crossref PubMed Scopus (37) Google ScholarMSKCC26629 (76/266)100‡These studies only evaluated primary truncal melanomas.2 (4/266)NoDecreased DFS and OS-Breslow thickness-SLN metastasis-UlcerationMcHugh, 20062McHugh J.B. Su L. Griffith K.A. et al.Significance of multiple lymphatic basin drainage in truncal melanoma patients undergoing sentinel lymph node biopsy.Ann Surg Oncol. 2006; 13: 1216-1223https://doi.org/10.1245/s10434-006-9014-zCrossref PubMed Scopus (32) Google ScholarUM42323 (98/423)100‡These studies only evaluated primary truncal melanomas.N/ANo-Younger age-Thicker lesions-Mitotic rateNoN/AMelstrom, 20149Melstrom L.G. Taylor E. Kuk D. et al.International multi-institutional management and outcome of melanoma patients with positive sentinel lymph nodes in more than one nodal basin.Ann Surg Oncol. 2014; 21: 4324-4329https://doi.org/10.1245/s10434-014-3845-9Crossref PubMed Scopus (10) Google ScholarMSKCC, MIA, UM97100†97 patients with at least one positive SLN in at least 2 lymphatic drainage basins.70 (68/97)100†97 patients with at least one positive SLN in at least 2 lymphatic drainage basins.N/AN/A-Positive SLN in MLBD associated with recurrent disease (56%)Howard, 20178Howard J.H. Ozao-Choy J.J. Hiles J.M. Sim M.S. Faries M.B. Prognostic value of multiple draining lymph node basins in melanoma: A matched-pair analysis based on the John Wayne Cancer Institute Experience.Front Oncol. 2017; 7: 172https://doi.org/10.3389/fonc.2017.00172Crossref PubMed Scopus (6) Google ScholarJWCI259100∗This study was a propensity matched-pair analysis in which 259 patients with MLBD were paired with 259 patients with single lymphatic basin drainage.87 (226/259)7 (17/259)NoNo-Higher T-stage-Ulceration-Older age-Lymph node positivityRibero, 20173Ribero S. Osella Abate S. Pasquali S. et al.Multiple lymph node basin drainage in trunk melanoma is not associated with survival of sentinel lymph node-positive patients.Dermatology. 2017; 233: 205-211https://doi.org/10.1159/000477457Crossref PubMed Scopus (4) Google ScholarUT31235 (108/312)100‡These studies only evaluated primary truncal melanomas.N/AYesNo-Thicker tumors-Ulceration-Number of positive lymph nodesa/w, Associated with; DFS, disease free survival; JWCI, John Wayne Cancer Institute; MDACC, M.D. Anderson Cancer Center; MIA, Melanoma Institute of Australia; MLBD, multiple lymphatic basin drainage; MSKCC, Memorial Sloan Kettering Cancer Center; OS, overall survival; SLN, sentinel lymph nodes; UIC, University of Illinois at Chicago; UM, University of Michigan; UT, University of Turin, 6 Italian referral centers.∗ This study was a propensity matched-pair analysis in which 259 patients with MLBD were paired with 259 patients with single lymphatic basin drainage.† 97 patients with at least one positive SLN in at least 2 lymphatic drainage basins.‡ These studies only evaluated primary truncal melanomas. Open table in a new tab a/w, Associated with; DFS, disease free survival; JWCI, John Wayne Cancer Institute; MDACC, M.D. Anderson Cancer Center; MIA, Melanoma Institute of Australia; MLBD, multiple lymphatic basin drainage; MSKCC, Memorial Sloan Kettering Cancer Center; OS, overall survival; SLN, sentinel lymph nodes; UIC, University of Illinois at Chicago; UM, University of Michigan; UT, University of Turin, 6 Italian referral centers. Melanoma SLN positivity in 2 or more lymphatic drainage basins is relatively uncommon, with an overall reported incidence of 3% to 7% (Table I).4Jacobs I.A. Chang C.K. Salti G.I. Significance of dual-basin drainage in patients with truncal melanoma undergoing sentinel lymph node biopsy.J Am Acad Dermatol. 2003; 49: 615-619https://doi.org/10.1067/S0190-9622(03)01838-3Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar, 5Jimenez R.E. Panageas K. Busam K.J. Brady M.S. Prognostic implications of multiple lymphatic basin drainage in patients with truncal melanoma.J Clin Oncol. 2005; 23: 518-524https://doi.org/10.1200/JCO.2005.00.075Crossref PubMed Scopus (37) Google Scholar, 6Porter G.A. I R.M. Berman R.S. Lee J.E. Mansfield P.F. Gershenwald J.E. Significance of multiple nodal basin drainage in truncal melanoma patients undergoing sentinel lymph node biopsy.Ann Surg Oncol. 2000; 7: 256-261https://doi.org/10.1007/s10434-000-0256-xCrossref PubMed Scopus (79) Google Scholar, 7Dale P.S. Foshag L.J. Wanek L.A. Morton D.L. Metastasis of primary melanoma to two separate lymph node basins: Prognostic significance.Ann Surg Oncol. 1997; 4: 13-18https://doi.org/10.1007/BF02316805Crossref PubMed Google Scholar, 8Howard J.H. Ozao-Choy J.J. Hiles J.M. Sim M.S. Faries M.B. Prognostic value of multiple draining lymph node basins in melanoma: A matched-pair analysis based on the John Wayne Cancer Institute Experience.Front Oncol. 2017; 7: 172https://doi.org/10.3389/fonc.2017.00172Crossref PubMed Scopus (6) Google Scholar Data on the prognostic significance of patients with positive SLN metastasis in MLBD is limited. Dale et al7Dale P.S. Foshag L.J. Wanek L.A. Morton D.L. Metastasis of primary melanoma to two separate lymph node basins: Prognostic significance.Ann Surg Oncol. 1997; 4: 13-18https://doi.org/10.1007/BF02316805Crossref PubMed Google Scholar found that in patients who underwent dissections of 2 or more lymphatic basins, positive SLN in MLBD was associated with decreased 1-, 3-, and 5-year and median survival. Melstrom et al9Melstrom L.G. Taylor E. Kuk D. et al.International multi-institutional management and outcome of melanoma patients with positive sentinel lymph nodes in more than one nodal basin.Ann Surg Oncol. 2014; 21: 4324-4329https://doi.org/10.1245/s10434-014-3845-9Crossref PubMed Scopus (10) Google Scholar found that 56% of patients with positive SLN in MLBD developed recurrent disease (the majority of recurrences were distant metastasis). Moreover, patients with stage IIIA and IIIB melanoma with metastasis in MLBD had a median survival of 41 months—a prognosis comparable to stage IIIC disease.9Melstrom L.G. Taylor E. Kuk D. et al.International multi-institutional management and outcome of melanoma patients with positive sentinel lymph nodes in more than one nodal basin.Ann Surg Oncol. 2014; 21: 4324-4329https://doi.org/10.1245/s10434-014-3845-9Crossref PubMed Scopus (10) Google Scholar Although these studies suggest a worse prognosis in patients with positive SLNs in MLBD, whether this poses an increased risk for further metastasis or mortality compared with positive SLN in single lymphatic basin drainage remains unclear.2McHugh J.B. Su L. Griffith K.A. et al.Significance of multiple lymphatic basin drainage in truncal melanoma patients undergoing sentinel lymph node biopsy.Ann Surg Oncol. 2006; 13: 1216-1223https://doi.org/10.1245/s10434-006-9014-zCrossref PubMed Scopus (32) Google Scholar,3Ribero S. Osella Abate S. Pasquali S. et al.Multiple lymph node basin drainage in trunk melanoma is not associated with survival of sentinel lymph node-positive patients.Dermatology. 2017; 233: 205-211https://doi.org/10.1159/000477457Crossref PubMed Scopus (4) Google Scholar,5Jimenez R.E. Panageas K. Busam K.J. Brady M.S. Prognostic implications of multiple lymphatic basin drainage in patients with truncal melanoma.J Clin Oncol. 2005; 23: 518-524https://doi.org/10.1200/JCO.2005.00.075Crossref PubMed Scopus (37) Google Scholar,8Howard J.H. Ozao-Choy J.J. Hiles J.M. Sim M.S. Faries M.B. Prognostic value of multiple draining lymph node basins in melanoma: A matched-pair analysis based on the John Wayne Cancer Institute Experience.Front Oncol. 2017; 7: 172https://doi.org/10.3389/fonc.2017.00172Crossref PubMed Scopus (6) Google Scholar Optimal management for patients with positive SLNs in MLBD basins will require further research. None disclosed.