Mitotic rate in primary melanoma: interobserver and intraobserver reliability, analyzed using H&E sections and immunohistochemistry.
BACKGROUND
In 2009, the AJCC issued a revised melanoma staging system. In addition to tumor thickness and ulceration, the mitotic rate was introduced as the third major prognostic parameter for the classification of primary cutaneous melanoma. Given that, according to the 2009 AJCC classification, the detection of one or more dermal tumor mitoses leads to an upstaging - from stage Ia to Ib - of melanomas with a tumor thickness of ≤ 1.0 mm, we set out to investigate the reproducibility of this new parameter.


METHODS
In order to assess interobserver reliability, 17 dermatopathologists und pathologists - all well versed in the diagnosis of cutaneous melanoma - analyzed the mitotic rate in 15 thin primary cutaneous melanomas (mean tumor thickness 0.91 mm) using identical slides. Mitotic rates were determined on H&E and phosphohistone H3 (Ser10)-stained samples. Without knowledge of their previous assessment, five of the aforementioned examiners reevaluated the samples after more than one year in order to ascertain intraobserver reliability.


RESULTS
Interobserver reliability of the mitotic rate in thin primary melanomas is disappointing and independent of whether H&E or immunohistochemically stained samples are used (kappa value: 0.088 [H&E], 0.154 [IH], respectively). Kappa values improved to 0.345 (H&E) and 0.403 (IH) when using a cutoff of 0/1 vs. 2+ mitoses. Similarly unsatisfactory, kappa values for intraobserver reliability ranged from 0.18 and 0.348, depending on the individual examiner.


CONCLUSIONS
Given the unsatisfactory reproducibility and large variations in assessing the mitotic rate, it remains a matter of debate whether this diagnostic parameter should play a role in therapeutic decisions.
Department of Dermatology, University Hospital, Tübingen, Germany. claus.garbe@med.uni-tuebingen.de.
Claus
C
Garbe
Department of Dermatology, University Hospital, Tübingen, Germany.
Thomas K
TK
Eigentler
Department of Dermatology, University Hospital, Tübingen, Germany.
Jürgen
J
Bauer
Dermatologicum Hamburg, Germany.
Norbert
N
Blödorn-Schlicht
Department of Dermatology and Venereology, University Hospital, Graz, Austria.
Lorenzo
L
Cerroni
Institute for Pathology, General Pathology, and Anatomic Pathology, Tübingen, Germany.
Falko
F
Fend
Dermatopathology Practice Friedrichshafen/Lake Constance, Friedrichshafen, Germany.
Markus
M
Hantschke
Department of Dermatology and Venereology, University Hospital, since 2014 HKS - Hautärzte Köln Süd, Dermatology Practice. Cologne, Cologne, Germany.
Peter
P
Kurschat
Dermatopathology Practice Friedrichshafen/Lake Constance, Friedrichshafen, Germany.
Heinz
H
Kutzner
Department of Dermatology, University Hospital, Münster, Germany.
Dieter
D
Metze
Dermatological Practice am Tibarg, Hamburg, Germany.
Volker
V
Mielke
Institute for Pathology, General Pathology, and Anatomic Pathology, Tübingen, Germany.
Harald
H
Preßler
Dermatological Practice am Tibarg, Hamburg, Germany.
Michael
M
Reusch
Dermatological Practice am Tibarg, Hamburg, Germany.
Ursula
U
Reusch
Department of Dermatology, Venereology, Allergology, and Phlebology, Johannes Wesling Hospital, Minden, Germany.
Rudolf
R
Stadler
Department of Dermatology, Venereology, and Allergolgy, HELIOS Hospital, Hildesheim, Germany.
Michael
M
Tronnier
Department of Dermatology, University Hospital, Tübingen, Germany.
Amir
A
Yazdi
Department of Dermatology, University Hospital, Tübingen, Germany.
Gisela
G
Metzler
D006801:Humans; D007150:Immunohistochemistry; D008545:Melanoma / Q000473:pathology*; D008940:Mitotic Index; D009367:Neoplasm Staging; D011379:Prognosis; D015203:Reproducibility of Results; D012878:Skin Neoplasms / Q000473:pathology*