M. Miettinen et al., Microphthalmia transcription factor in the immunohistochemical diagnosis of metastatic melanoma - Comparison with four other melanoma markers, AM J SURG P, 25(2), 2001, pp. 205-211
Citations number
38
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research Diagnosis & Treatment
The diagnosis of metastatic malignant melanoma (MMM) may be difficult in su
rgical pathology, often complicated by the unpredictable spread of this tum
or and its great variability on histologic evaluation. Traditionally used i
mmunohistochemical markers on melanomas are insufficient because of either
a relative lack of specificity (S100 protein) or variably reported sensitiv
ity (HMB45). Information about some newer markers. such as tyrosinase (TYR)
and Melan A, is more limited. Recently, based on the study of a small numb
er of tumors, it was suggested that microphthalmia transcription factor (MI
TF) is 100% sensitive in the identification of metastatic melanoma. In the
current study, we compared the diagnostic usefulness of MITF with that of f
our other markers in 266 cases of conventional metastatic melanomas from di
fferent sites, 33 cases of desmoplastic melanomas, and 1 case of melanoma w
ith rhabdoid features. The specificity of MITF was evaluated by using a rep
resentative sample of control tumors. Microphthalmia transcription factor w
ith nuclear positivity was seen in 235 of 266 cases of conventional MMM (88
%), usually in more than 30% of tumor cells. However, some melanomas had on
ly foci of MITF- and TYR-positive cells, whereas the majority of cells were
generally S100 protein-positive. Only 1 of 30 desmoplastic melanomas (3%)
had MITF-positive cells, representing epithelioid foci resembling conventio
nal melanoma. Two cases had TYR in a similar pattern: all were HMB45-negati
ve. One metastatic melanoma with rhabdoid features was negative for MITF an
d other markers except the S100 protein. Half of the S100 protein negative
conventional melanomas (6 of 12) were MITF-positive, whereas 4 of 20 (20%)
TYR-negative tumors had reactivity for MITF. The percentages of positive ca
sts of MMM (10% or more tumor cells positive) diagnosed with the four other
markers in descending order were 90% (S100 protein and TYR), 78% (melan-A)
, and 66% (HMB45). Microphthalmia transcription factor appeared to be speci
fic, because significant reactivity was not found in 112 carcinomas, 20 lym
phomas, 20 angiosarcomas, 20 fibrous histiocytomas, and 20 malignant periph
eral nerve sheath tumors. However, positive nuclei were found focally among
reactive histiocytes, especially in osteoclasts, epithelioid histiocytes,
and sporadic other histiocytes. Microphthalmia transcription factor may be
a valuable addition to the marker panel used in diagnosing melanoma, in com
bination with S100, TYR, and the other markers, but it is not present in ca
ses of desmoplastic melanomas.