SOX10 Expression Distinguishes Desmoplastic Melanoma From Its Histologic Mimics
Department of Pathology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA. The American Journal of dermatopathology
(Impact Factor: 1.39).
01/2013; 35(5). DOI: 10.1097/DAD.0b013e31827a0b98
Desmoplastic melanoma (DM) presents diagnostic challenges due to histologic mimics and limited immunohistochemical staining. Although S100 usually stains DM, other melanoma markers (HMB-45 and Melan-A) are often negative. Dermal/subcutaneous mimics of DM [spindle cell/poorly differentiated squamous cell carcinoma, atypical fibroxanthoma (AFX), and sarcoma] show negative or unreliable immunohistochemical staining. Recently, SOX10 expression has been shown to be a sensitive and specific marker of DM. However, there are no published studies comparing the sensitivity and specificity of SOX10 for DM compared with its most common histologic mimics of the dermis/subcutis. We examined 76 cases, including DM (n = 15), spindle cell/poorly differentiated carcinoma (n = 18), AFX (n = 13), sarcoma with spindled morphology (n = 20), and malignant peripheral nerve sheath tumor (MPNST) (n = 10). Most (75%, 15/20) of sarcomas were centered in the dermis/subcutis and included sarcoma not otherwise specified, DFSP with sarcomatous transformation and myxofibrosarcoma. SOX10 was diffusely positive in 100% (15/15) of DMs and showed focal staining in 30% (3/10) of MPNSTs. All other tumors were negative for SOX10 [0% (0/18) of carcinomas, 0% (0/13) of AFXs, 0% (0/20) of sarcomas]. In conclusion, SOX10 is a highly useful marker to confirm the diagnosis of DM. In our study, SOX10 showed 100% sensitivity for DM and SOX10 was negative in all histologic mimics of the dermis/subcutis, including spindle cell carcinoma, AFX and sarcomas. Similar to S-100 protein, some MPNSTs show scattered positivity but did not show diffuse positivity seen in DM.
Available from: Roman Mezencev
- "In neoplasms, nuclear SOX10 expression is found in benign melanocytic lesions and all melanoma subtypes (Nonaka et al., 2008; Shin et al., 2012; Mohamed et al., 2013), including diagnostically challenging cases of desmoplastic melanoma (Ramos-Herberth et al., 2010; Palla et al., 2013) and metastatic melanoma (Blochin and Nonaka, 2009; Jennings and Kim, 2011), with sensitivity in various studies approaching 100%. Most epithelial neoplasms tested so far have been SOX10 negative, except for (i) a proportion of breast carcinomas, primarily in the basal-like, triple negative and metaplastic subgroups (Mohamed et al., 2013; Cimino-Mathews et al., 2013; Ivanov et al., 2013) and (ii) salivary gland tumors (acinic cell carcinoma, adenoid cystic carcinoma, epithelial-myoepithelial carcinoma, myoepithelioma and myoepithelial carcinoma and pleomorphic adenoma) (Nonaka et al., 2008; Ivanov et al., 2013; Ohtomo et al., 2013). "
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ABSTRACT: SOX10 belongs to the family of transcription factors essential for the development of neural crest, peripheral nervous system and melanocytes. It is presently used in histopathology as a marker of melanocytic differentiation. SOX10 is expressed in normal brain tissue in oligodendrocytes, but the information about SOX10 expression in primary tumors of the central nervous system is quite limited. In this study, we examined the expression of SOX10 and Olig2 by immunohistochemistry in a series of 98 glial tumors and explored their specificity and sensitivity for differential diagnosis of ependymal vs non-ependymal tumors. In addition, we examined the expression of EMA and CD99 in ependymal tumors. SOX10 and Olig2 staining were scored as negative if no positive cells or only a few positive cells (typically up to 1-3%) were found. In all other instances, SOX10 or Olig2 staining was scored as positive. Out of 44 examined ependymal tumors none was found to express SOX10 and 7 specimens showed only a few SOX10-positive cells that likely corresponded to entrapped non-neoplastic oligodendrocytes. In contrast, non-ependymal tumors expressed SOX10 in 26/54 (48%) specimens. Olig2 was positive in 5 out of 44 ependymomas (11%) and 50 out of 54 (93%) non-ependymal tumors (astrocytomas and oligodendrogliomas). EMA and CD99 expression was found in 33/44 (75%) and 11/44 (25%) of ependymomas, respectively. SOX10-positivity rules out the diagnosis of ependymoma among other glial tumors with high confidence.
Histology and histopathology 08/2015; DOI:10.14670/HH-11-654 · 2.10 Impact Factor
Available from: archivesofpathology.org
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ABSTRACT: Approximately 25% of patients with breast cancer develop cutaneous metastases. Sweat gland carcinomas (SGCs) account for about 0.05% of all cutaneous neoplasms. Cutaneous metastases of breast carcinoma (CMBCs) (especially the ductal type) can be difficult to distinguish from SGCs. Treatment and prognoses for these 2 types of tumors differ radically, making accurate histologic diagnosis crucial. Although a few studies attempt to differentiate these entities employing immunohistochemical (IHC) studies (some of which we review here), to date, no panel of IHC stains exists, to our knowledge, to distinguish these entities.
To devise a panel of IHC stains to distinguish CMBC from SGC.
Twelve cases of ductal CMBCs (11 not otherwise specified type, and 1 basal phenotype), 11 cases of SGCs (5 eccrine carcinomas, 3 porocarcinomas, and 3 microcystic adnexal carcinomas), 2 benign sweat gland neoplasm cases, and 2 primary breast cancer cases were retrieved and analyzed with the following IHC panel: mammaglobin, gross cystic disease fluid protein (GCDFP) 15, p63, basal cytokeratins (CK5, CK14, and CK17), androgen receptor, and PAX5.
The p63 was only weakly expressed in 1 of 12 CMBC cases (8.3%), whereas it was strongly expressed in 10 of 11 SGC cases (90.9%) (P < .001). Basal cytokeratins demonstrated a similar immunoprofile in the SGC group, with 10 of 11 cases (90.9%) expressing all 3 markers, and a variable immunoprofile in the CMBC group with 0% (CK14) (P < .001) to 16.7% (2 of 12 cases; CK5 and CK17) (P < .001) expression. Mammaglobin was expressed in 8 of 12 cases (66.7%) of CMBC.
Together, these 5 IHC stains were combined to make a panel that was 100% sensitive and 91% specific in distinguishing between CMBC and SGC.
Archives of pathology & laboratory medicine 08/2011; 135(8):975-83. DOI:10.5858/2009-0445-OAR2 · 2.84 Impact Factor
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ABSTRACT: Cutaneous squamous cell carcinoma (cSCC) is a concerning toxicity with BRAF inhibitors in the treatment of melanoma. While the two drugs shown to improve survival, vemurafenib and dabrafenib, have similar efficacy, the reported rates of cSCC are quite different. Drawing upon pre-clinical and clinical trial data, this article discusses the potential factors behind the different cSCC incidences reported with the two BRAF inhibitors, and provides a strategic approach to understand this issue further.Significance. While cSCCs themselves may not be a major clinical problem in the metastatic setting, they are of greater importance as BRAF inhibitors enter adjuvant treatment, particularly as they point to a wider issue of the oncogenic propensity of these drugs. Emerging reports of non-cutaneous malignancies propagated by BRAF inhibitors are of concern, especially as they are thought to be driven by the same process that leads to cSCC. The true relative prevalence of cSCCs with vemurafenib and dabrafenib may inform the relative risk of other non-cutaneous malignancies with these drugs, which should serve to influence clinical management and drug design. This article is protected by copyright. All rights reserved.
Pigment Cell & Melanoma Research 06/2013; 26(5). DOI:10.1111/pcmr.12132 · 4.62 Impact Factor
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