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Apolipoprotein D in CD34-positive and CD34-negative cutaneous
neoplasms: a useful marker in differentiating superficial acral
fibromyxoma from dermatofibrosarcoma protuberans.Mod
Pathol. 2008 Jan;21(1):31-8. Epub 2007 Sep 21.
More recent
techniques to characterize the genetic profile of soft-tissue tumors
include the use of gene arrays. Using this technique, Apolipoprotein D
(Apo D), a 33-kDa glycoprotein component of high-density lipoprotein,
has been found to be highly expressed in dermatofibrosarcoma
protuberans. To corroborate these results, we sought to ascertain the
utility of Apo D by investigating its sensitivity and specificity in a
variety of CD34-positive and CD34-negative cutaneous neoplasms
including superficial acral fibromyxoma, sclerotic fibromas, and
cellular dermatofibromas. Of interest, we found absence of Apo D
expression in all four cases of superficial acral fibromyxoma. Of the
remaining CD34-positive lesions, Apo D expression was noted in 35/36
(97%) cases of dermatofibrosarcoma protuberans, 3/5 (60%) giant-cell
fibroblastomas, 4/4 (100%) sclerotic fibromas, 8/8 (100%)
neurofibromas, and 1/1 (100%) solitary fibrous tumor. Of the
CD34-negative lesions, Apo D expression was noted in 2/22 (9%) regular
dermatofibroma, 23/45 (51%) cellular dermatofibroma, 10/10 (100%)
malignant fibrous histiocytoma, 9/10 (90%) atypical fibroxanthoma, 7/8
(86%) cellular neurothekeoma, 9/9 (100%) malignant melanoma, 8/8
(100%) melanocytic nevi (100%), 0/2 superficial angiomyxoma, 0/15
fibromatosis, 0/1 nodular fasciitis, and 1/2 (50%) desmoplastic
fibroblastomas. In summary, our findings indicate that Apo D
expression is not specific to dermatofibrosarcoma protuberans. Its
principal use as an immunohistochemical adjunct lies in its utility in
differentiating superficial acral fibromyxoma from dermatofibrosarcoma
protuberans. Although strong positive staining of Apo D in a markedly
atypical fibrohistiocytic lesion is suggestive of atypical
fibroxanthoma and/or malignant fibrous histiocytoma, further studies
with the inclusion of other atypical spindled cell neoplasms are
required to conclusively prove the same. |
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Dermatofibrosarcoma Protuberans
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Dermpath-India
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Dermatofibrosarcoma protuberans COL1A1-PDGFB fusion is identified in
virtually all dermatofibrosarcoma protuberans cases when
investigated by newly developed multiplex reverse transcription
polymerase chain reaction and fluorescence in situ hybridization
assays.
Dermatofibrosarcoma protuberans (DFSP) is a cutaneous, locally
aggressive spindle cell tumor of intermediate malignancy. Tumor
cells are reactive for CD34 and characterized by a t(17;22)
translocation or a supernumerary ring chromosome that results in the
fusion of exon 2 of PDGFB to various exons of the COL1A1 gene. We
developed a multiplex reverse transcription polymerase chain
reaction (RT-PCR) assay to detect fusion transcripts for all
possible COL1A1 breakpoints. Twenty-seven formalin-fixed,
paraffin-embedded DFSP cases were analyzed using 18 COL1A1 forward
primers and 1 exon 2 PDGFB reverse primer. Sequence analysis was
performed to definitively characterize breakpoints. Results were
correlated with histology, immunohistochemistry, PDGFB break-apart
fluorescence in situ hybridization analysis, and cytogenetics when
available. Fusion transcripts were detected by RT-PCR in all but one
DFSP case. Sequencing revealed a PDGFB exon 2 breakpoint in all
cases. COL1A1 breakpoints were in exons 7 (1 patient), 10 (1), 29
(2), 40 (1), 46 (3), and 49 (2), and intronic between exons 13:14
(1), 26:27 (2), 30:31 (1) 33:34 (1), 43:44 (7), 45:46 (1), and 46:47
(1). Three novel COL1A1 breakpoints were identified, intronic
between exons 13:14 (1), 30:31 (1) and in exon 49 (2). There was no
correlation found between breakpoints and age, sex, or histologic
variants. Using this sensitive multiplex RT-PCR assay in combination
with fluorescence in situ hybridization, we found COL1A1-PDGFB
rearrangements appear more prevalent in DFSP than previously
reported. Its detection may be particularly helpful in the
differential diagnosis of atypical, fibrosarcomatous, and metastatic
DFSP. |
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June 2009
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