A. Hafeez Diwan

Immunodeficiency-related lymphoproliferative disorders (IR-LPD) may occur in the setting of immunosuppressive therapy with methotrexate and TNF-α antagonists. As far as we are aware, this is the first report of an Epstein-Barr virus-associated B-cell lymphoproliferative disorder, secondary to methotrexate therapy in a patient with mycosis fungoides/Sézary syndrome.

According to most authors, dermatofibrosarcoma protuberans (DFSP) and giant cell fibroblastoma (GCF) represent the adult and juvenile forms, respectively, of the same disease entity, as evidenced by similar morphology, an identical chromosomal translocation, and CD34 positivity. It has been shown that DFSP and nuchal‐type fibroma (NTF) (which is also CD34‐positive) are related lesions, and that there might possibly be a continuum between the two. In addition, NTF exhibits CD99 positivity. It was therefore, hypothesized that both DFSP and GCF would show similar immunopositivity for CD99. Archives of pathology at several institutions were searched for DFSP and GCF tissue blocks. A total of 29 DFSP and 5 GCF were analyzed by immunohistochemistry for expression of CD99. Twenty‐three of 29 DFSP (79%) and 2 of 5 GCP (40%) expressed CD99. Comparison of CD99 and CD34 showed that the non‐tumoral periphery of DFSP was less probable to be CD99 positive, but this finding was not statistically significant.

Background: Protein tyrosine kinase (PTK) inhibition has been identified as a promising strategy in the development of new selective therapies, targeting the signaling pathways in melanoma progression. Gleevec, a novel class of anti-tumor drugs, may have a potential therapeutic benefit in melanoma, which involves abnormal activation of abl, c-kit, and platelet-derived growth factor (PDGF) tyrosine kinases. Methods: Tumor biopsies from 13 patients with metastatic melanoma were screened by immunohistochemistry for PTK [c-kit, C-abl, Abl-related gene (ARG), PDGF receptor-α (PDGFR-α) and PDGFR-β] expression before and after being treated with Gleevec @ 400 mg bid for 2 weeks. Both, percentage of positive cells and staining intensity were evaluated. Results: We found a statistically significant (p < 0.01) selective loss of PTK expression in the follow-up biopsy, both in intensity and number of positive cells. PDGFR-α and -β had the highest level of expression reduction. One patient had a durable clinical response, and the follow-up biopsy showed negative expression for four of the PTKs, namely c-abl, ARG, PDGFR-α, and β. Conclusions: Our study reports for the first time the in vivo effect of Gleevec in the induction of apparently selective reduction of PTKs expression under anti-tyrosine kinases treatment, suggesting its potential role in melanoma treatment.

BACKGROUND: Expression of the antiapoptotic protein survivin has been demonstrated in some melanocytic lesions and is believed to be required for melanoma cell viability. However, its diagnostic value in differentiating melanomas from nevi has not yet been examined.METHODS: Tissue microarray blocks were constructed with paraffin‐fixed tissue of 19 nevi, 18 dysplastic nevi, 24 malignant melanomas, and 31 metastatic melanomas. Sections were then reacted with three antisurvivin antibodies (two monoclonal and one polyclonal) assessing labeling intensity (absent or weak, and moderate to strong) as well as the percentage of cells labeled (< 25%, ≥ 25%).RESULTS: Of the antibodies evaluated, the polyclonal one was found to be the most sensitive. Nuclear immunoreactivity for survivin (i.e., ≥ 25% of cells exhibiting and/or at least moderately intense staining) was seen in a subset of melanomas but not in nevi or dysplastic nevi (P < 0.05)CONCLUSIONS: Survivin is variably expressed in the cytoplasm in the entire spectrum of melanocytic lesions, with nuclear expression detectable only in melanomas. These data may underscore the importance of nuclear survivin in progression to melanoma and may prove useful in the differential diagnosis of melanoma versus nevus. Cancer 2006. © 2006 American Cancer Society.