title: Histological pattern of Merkel cell carcinoma sentinel lymph node metastasis improves stratification of Stage III patients.
abstract: Sentinel lymph node biopsy is used to stage Merkel cell carcinoma, but its prognostic value has been questioned. Furthermore, predictors of outcome in sentinel lymph node positive Merkel cell carcinoma patients are poorly defined. In breast carcinoma, isolated immunohistochemically positive tumor cells have no impact, but in melanoma they are considered significant. The significance of sentinel lymph node metastasis tumor burden (including isolated tumor cells) and pattern of involvement in Merkel cell carcinoma are unknown. In this study, 64 Merkel cell carcinomas involving sentinel lymph nodes and corresponding immunohistochemical stains were reviewed and clinicopathological predictors of outcome were sought. Five metastatic patterns were identified: (1) sheet-like (n=38, 59%); (2) non-solid parafollicular (n=4, 6%); (3) sinusoidal, (n=11, 17%); (4) perivascular hilar (n=1, 2%); and (5) rare scattered parenchymal cells (n=10, 16%). At the time of follow-up, 30/63 (48%) patients had died with 21 (33%) attributable to Merkel cell carcinoma. Patients with pattern 1 metastases had poorer overall survival compared with patients with patterns 2-5 metastases (P=0.03), with 22/30 (73%) deaths occurring in pattern 1 patients. Three (10%) deaths occurred in patients showing pattern 5, all of whom were immunosuppressed. Four (13%) deaths occurred in pattern 3 patients and 1 (3%) death occurred in a pattern 2 patient. In multivariable analysis, the number of positive sentinel lymph nodes (1 or 2 versus >2, P<0.0001), age (<70 versus ≥70, P=0.01), sentinel lymph node metastasis pattern (patterns 2-5 versus 1, P=0.02), and immune status (immunocompetent versus suppressed, P=0.03) were independent predictors of outcome, and could be used to stratify Stage III patients into three groups with markedly different outcomes. In Merkel cell carcinoma, the pattern of sentinel lymph node involvement provides important prognostic information and utilizing this data with other clinicopathological features facilitates risk stratification of Merkel cell carcinoma patients who may have management implications.
authors.affiliation: Department of Pathology, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Ko
authors.affiliation: Department of Pathology, MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Victor G
authors.initials: VG
authors.lastname: Prieto
authors.affiliation: Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Elson
authors.affiliation: Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney; Melanoma Institute Australia, North Sydney; Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Ricardo E
authors.initials: RE
authors.lastname: Vilain
authors.affiliation: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
authors.forename: Melissa P
authors.initials: MP
authors.lastname: Pulitzer
authors.affiliation: Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney; Melanoma Institute Australia, North Sydney; Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Scolyer
authors.affiliation: Department of Pathology, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Jordan P
authors.initials: JP
authors.lastname: Reynolds
authors.affiliation: Department of Pathology, Cleveland Clinic, Cleveland, Ohio, USA.|Department of Dermatology, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Melissa P
authors.initials: MP
authors.lastname: Piliang
authors.affiliation: Department of Hematology Oncology, Melanoma Program, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Marc S
authors.initials: MS
authors.lastname: Ernstoff
authors.affiliation: Department of Plastic Surgery, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Gastman
authors.affiliation: Department of Pathology, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Billings
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D015266:Carcinoma, Merkel Cell / Q000737:chemistry / Q000276:immunology / Q000401:mortality / Q000556:secondary* / Q000628:therapy; D016009:Chi-Square Distribution; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D018570:Risk Assessment; D012307:Risk Factors; D021701:Sentinel Lymph Node Biopsy; D012878:Skin Neoplasms / Q000737:chemistry / Q000276:immunology / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor