title: Proliferation indices correlate with diagnosis and metastasis in diagnostically challenging melanocytic tumors.
abstract: The diagnosis of melanocytic lesions remains a formidable challenge in dermatopathology. For diagnostically challenging lesions, ancillary tests are available to inform the diagnosis, including immunohistochemistry and molecular testing (particularly fluorescence in situ hybridization [FISH]). However, the test result that most robustly informs the diagnosis remains controversial. Thirty-seven diagnostically challenging melanocytic lesions from our consultation service were reviewed. Histopathologic, immunohistochemical, and second-generation FISH results (NeoGenomics; probes 6p25, 8q24, 11q13, 9p21, and centromere 9) were correlated with the final consensus diagnosis and clinical follow-up using logistic regression and Fisher exact test. Based on histopathologic and immunohistochemical features, cases were designated as "favor benign" (n=19) or "favor malignant" (n=18) by a consensus group of up to 7 dermatopathologists. The sensitivity of FISH for the diagnosis of melanoma was 39%, and the specificity was 84%. Univariate logistic regression models for a final diagnosis of melanoma showed that only increased Ki-67-positive dermal tumor cells (≥5%; P=.01) significantly correlated with the diagnosis of melanoma. FISH result did not correlate with the final diagnosis (melanoma or nevus; P=.26). Follow-up (range, 8-29months) was available for 35 cases (19 diagnosed as nevus and 16 as melanoma), and metastases (restricted to sentinel lymph nodes) were detected from 5 melanomas (3 FISH negative and 2 FISH positive). Only increased dermal mitotic figures (>1/mm(2)) correlated with metastases to sentinel lymph nodes (P=.04). Thus, in the classification of diagnostically challenging melanocytic lesions, indices of proliferation emerge as the most informative diagnostic adjuncts-correlating with diagnosis and clinical behavior, respectively.
authors.affiliation: Department of Pathology, Section of Dermatopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Rami N
authors.initials: RN
authors.lastname: Al-Rohil
authors.affiliation: Department of Pathology, Section of Dermatopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Curry
authors.affiliation: Department of Pathology, Section of Dermatopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Torres-Cabala
authors.affiliation: Department of Pathology, Section of Dermatopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Priyadharsini
authors.initials: P
authors.lastname: Nagarajan
authors.affiliation: Department of Pathology, Section of Dermatopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Doina
authors.initials: D
authors.lastname: Ivan
authors.affiliation: Department of Pathology, Section of Dermatopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Phyu P
authors.initials: PP
authors.lastname: Aung
authors.affiliation: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Genevieve F
authors.initials: GF
authors.lastname: Lyons
authors.affiliation: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Roland L
authors.initials: RL
authors.lastname: Bassett
authors.affiliation: Department of Pathology, Section of Dermatopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: vprieto@mdanderson.org.
authors.forename: Victor G
authors.initials: VG
authors.lastname: Prieto
authors.affiliation: Department of Pathology, Section of Dermatopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Translational and Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: mtetzlaff@mdanderson.org.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Tetzlaff
mesh_terms: D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D049109:Cell Proliferation; D002648:Child; D002906:Chromosomes, Human, 6-12 and X; D002880:Chromosomes, Human, Pair 11; D002898:Chromosomes, Human, Pair 8; D002899:Chromosomes, Human, Pair 9; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D019394:Ki-67 Antigen / Q000032:analysis*; D016015:Logistic Models; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000556:secondary; D058950:Melanoma-Specific Antigens / Q000032:analysis*; D008875:Middle Aged; D008940:Mitotic Index; D009508:Nevus, Pigmented / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D015203:Reproducibility of Results; D012878:Skin Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D013997:Time Factors; D055815:Young Adult; D058951:gp100 Melanoma Antigen
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D058950:Melanoma-Specific Antigens; C548637:PMEL protein, human; D058951:gp100 Melanoma Antigen
keywords: Diagnostically challenging melanocytic lesions; Fluorescence in situ hybridization; Immunohistochemistry; Melanoma; Nevus