2016, Volume 32, Number 1, Page(s) 063-064
Diagnostic Disputes Regarding Atypical Melanocytic Lesions can be Solved by Using the Term MELTUMP
Francesco PISCIOLI, Teresa PUSIOL, Luca RONCATI
Provincial Health Care Services, Institute of Pathology, Santa Maria del Carmine Hospital, ROVERETO (TN), ITALY
To the Editor,
Melanocytic tumors of unknown malignant potential
(MELTUMPs) are melanocytic lesions that cannot be
classified as either benign or malignant tumors. In fact,
they have ambiguous characteristics that reflect an
unclear biological potential. Several types of melanocytic
lesions may be classified as MELTUMPs: atypical Spitz
nevi / tumors, dysplastic nevi, pigmented epithelioid
melanocytoma, deep penetrating nevi, congenital nevi
with atypia, cellular nodules in congenital naevi, borderline
melanoma, minimal deviation melanoma, and dermalbased
borderline melanocytic tumors. By definition,
MELTUMP is a provisional diagnosis and it is necessary
to establish parameters that may suggest its most probable
clinical behavior. In our experience, the histopathological
report should include all the microstaging data for invasive
melanoma with the following adjuncts: presence or
absence of lymphatic invasion, result of fluorescence in situ
hybridization (FISH), histological criteria in according to
Cerroni and colleagues1, and second opinion consultation.
Lymphatic invasion (LI) is defined as S100 protein-positive
cells within a podoplanin-positive lymphatic space. This
dual immunohistochemical staining should be performed in
all cases of MELTUMP, because it can provide a prognostic
adjunct in determining whether those lesions are capable
of distant metastases and fatal outcomes2. The presence
of LI correlates with a more aggressive clinical outcome,
defined as developing nodal metastases, distant metastases,
or melanoma-related death2. Various studies have
demonstrated the utility of FISH as an ancillary method
in the diagnosis of ambiguous melanocytic neoplasms.
A panel of FISH targeting loci on chromosomes 6 and 11
has emerged as a powerful tool to discriminate melanoma
from nevi with a sensitivity and specificity of 87% and 96%,
respectively3. Early retrospective studies have shown
correlation between metastatic behavior among ambiguous
melanocytic lesions and FISH results4. FISH testing can
so help to reduce the number of equivocal diagnoses in
course of ambiguous melanocytic neoplasm, in particular
if FISH testing is positive. In the study of Cerroni et al.1,
75 cases of MELTUMP were classified within three groups
according to their behavior as follows: a) favorable (no
evidence of metastatic disease after a follow-up ≥ 5 years);
b) unfavorable (tumor-related death and/or large deposits in the lymphatic nodes and/or visceral metastases; c)
borderline (small nodal deposits of tumor cells ≤ 0.2 mm).
The only three histopathologic criteria that were statistically
different between the groups of unfavorable and favorable
cases were: presence of mitoses, mitoses near to the base
and an inflammatory reaction. All these features were
found more frequently in cases with unfavorable behavior.
In our experience5, the second opinion of Prof. Elder
and Prof. Murphy has permitted a better comprehension of
MELTUMP. We have read with great interest the clinicopathological
study of atypia and differential diagnosis in
cellular blue nevi (CBN) by Yaman et al.6, based on a
21-case series diagnosed between 2000-2014. Five patients
were assessed as ‘atypical cellular blue nevus’ (ACBN). A
6-cm-diameter tumor showed an infiltrative development;
two cases presented two mitoses and two MIB-1 labeling
indexes at 3% and 2%, respectively; a case was characterized
by one mitosis and a confluent development, and a case by
one mitosis with additional focal necrosis. No lymphatic
and/or distant metastases were observed during the followup.
Yaman et al. believe that there is no precise definition
of ACBN, but the term is used for CBN that has atypical
features and requires differentiation from malignant blue
nevus. The features of ACBN are widely studied in the
accurate review of blue nevi and variants by Zembowicz and
Phadke7. The authors believe that there are no established
consensus criteria regarding diagnostic category of ACBN.
This term is useful to identify histologically ambiguous
lesion and to convey out some uncertainty in relation to the
biological potential of the lesion, without overinterpreting
the tumor as an outright melanoma. Zembowicz and Mihm8 consider CBN as atypical when they are large (> 5-10 cm)
and ulcerated, they show marked nuclear pleomorphism,
and have more than 3 to 4 mitotic figures / square mm, and
either pushing or infiltrating margins. The authors argue
that unfortunately these features are not discriminating
and can also be found in conventional CBN, as well in
malignant blue nevus. In the opinion of Murali et al.9, the
pathological features of ACBN are as follows: size greater
than 3 cm, increased cellularity, cellular polymorphism
(focal areas of atypia in a background of CBN), increased
mitotic activity (but less than 2 mitoses / square mm), no
atypical mitoses and no areas of necrosis. In conclusion,
ACBN is a classic example of MELTUMP, because divergent opinions regarding histological features and clinical
behavior are present. The diagnosis of MELTUMP, referred
to as an atypical blue nevus, seems to be more appropriate
for determining an accurate management of the lesion.
1) Cerroni L, Barnhill R, Elder D, Gottlieb G, Heenan P, Kutzner
H, LeBoit PE, Mihm M Jr, Rosai J, Kerl H. Melanocytic
tumors of uncertain malignant potential: Results of a tutorial
held at the XXIX Symposium of the International Society of
Dermatopathology in Graz, October 2008. Am J Surg Pathol.
2) Abraham RM, Karakousis G, Acs G, Ziober AF, Cerroni L, Mihm
MC Jr, Elder DE, Xu X. Lymphatic invasion predicts aggressive
behavior in melanocytic tumors of uncertain malignant potential
(MELTUMP). Am J Surg Pathol. 2013;37:669-75.
3) North JP, Garrido MC, Kolaitis NA, LeBoit PE, McCalmont TH,
Bastian BC. Fluorescence in situ hybridization as an ancillary tool
in the diagnosis of ambiguous melanocytic neoplasms: A review
of 804 cases. Am J Surg Pathol. 2014;38:824-31.
4) Vergier B, Prochazkova-Carlotti M, de la Fouchardière A, Cerroni
L, Massi D, De Giorgi V, Bailly C, Wesselmann U, Karlseladze A,
Avril MF, Jouary T, Merlio JP. Fluorescence in situ hybridization,
a diagnostic aid in ambiguous melanocytic tumors: European
study of 113 cases. Mod Pathol. 2011;24:613-23.
5) Pusiol T, Morichetti D, Piscioli F, Zorzi MG. Theory and practical
application of superficial atypical melanocytic proliferations of
uncertain significance (SAMPUS) and melanocytic tumours
of uncertain malignant potential (MELTUMP) terminology:
Experience with second opinion consultation. Pathologica.
6) Yaman B, Kandiloglu G, Kumbaraci BS, Akalin T. Atypia and
differential diagnosis in cellular blue nevi: Clinicopathological
study of 21 cases. Turk Patoloji Derg. 2015;31:89-94.
7) Zembowicz A, Phadke PA. Blue nevi and variants: An update.
Arch Pathol Lab Med. 2011;135:327-36.
8) Zembowicz A, Mihm MC. Dermal dendritic melanocytic
proliferations: An update. Histopathology. 2004;45:433-51.
9) Murali R, McCarthy SW, Scolyer RA. Blue nevi and related
lesions: A review highlighting atypical and newly described
variants, distinguishing features and diagnostic pitfalls. Adv Anat