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Basal cell carcinoma (BCC) is classified histologically into subtypes that determine treatment decisions. MicroRNAs (miRs) are short noncoding RNAs that may serve as diagnostic biomarkers. We investigated if particular miRs could distinguish BCC subtypes. We sequenced miRs from 55 archival BCC and 9 control skin specimens and then validated these miRs by qRT-PCR assay on a second BCC cohort (18 superficial, 16 nodular, 15 infiltrative) and control skin (n = 12). Expression values for individual miRs were normalized to miR-16-5p, which was the least variant among the control skin and BCC samples. We found that (i) miR-383-5p and miR-145-5p are downregulated in all BCC subtypes compared with control skin, (ii) miR-181c-5p is downregulated in superficial compared with invasive (nodular/infiltrative) BCC, and (iii) miR-22-5p and miR-708-5p are upregulated in infiltrative compared with superficial/nodular BCC and miR-30c-5p is downregulated in infiltrative compared with nodular BCC. Receiver operating characteristic analysis demonstrated excellent capacity of these miRs to discriminate between BCC and control skin (area under the curve, 0.94–0.98), whereas the capacity to discriminate between superficial and invasive subtypes was less robust (area under the curve, 0.7–0.8). Future prospective studies may determine the utility of these miRs as diagnostic biomarkers to guide biopsy and treatment of BCC.

Abstract Background Cutaneous hypersensitivity eruptions in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) are a clinically and histologically heterogeneous group that can either precede, occur with, or follow the development of a hematologic malignancy. Therefore, establishing the diagnosis requires careful clinical and pathologic correlation and an understanding of the broad spectrum of presentations. Data is lacking on the correlation of skin disease with molecular/cytogenetic risk profiling of the tumor. Objectives The aims of this study were to characterize the clinical, histological, and genetic aberrations in recurrent cutaneous hypersensitivity reactions in patients with CLL/SLL. Methods A single site academic retrospective chart review of medical records, histopathology, molecular and cytogenetic data in CLL/SLL patients who developed biopsy‐proven cutaneous hypersensitivity reactions. Results Five hundred one new diagnoses of CLL/SLL with 73 patients requiring cutaneous biopsies for skin lesions or rashes were identified. With exclusion criteria, 20 biopsies were identified from 17 patients (mean age, 69.6 years, females = 9) with unexplained cutaneous eruptions. These were commonly pruritic, erythematous papules above the waist. Most biopsies had a prominent superficial, deep dermal eosinophilic infiltrate (85%), with a robust T‐cell predominant dermal infiltrate in 40%. Five out of 17 patients (29%) had a predominately folliculocentric CD4+ T‐cell infiltrate; all occurring on the head and neck. Overall, the prevalence of cutaneous hypersensitivity eruptions requiring biopsy was 3.4% (n = 17), and the prevalence of folliculocentric CD4+ T‐cell infiltrate was 1% (n = 5). Conclusion Cutaneous hypersensitivity reactions in CLL/SLL are heterogeneous; however, folliculotropic CD4+ T‐cell infiltrates may be seen in a small but distinct clinical subset of patients. Commonly tested cytogenetic aberrations in CLL/SLL do not appear to be correlated with the presence of cutaneous hypersensitivity reactions.

There are no currently available low-cost, noninvasive methods for discerning the depth of squamous cell carcinoma (SCC) invasion or distinguishing SCC from its benign mimics, such as inflamed seborrheic keratosis (SK). We studied 35 subjects with subsequently confirmed SCC or SK. Subjects underwent electrical impedance dermography measurements at six frequencies to assess the electrical properties of the lesion. Averaged greatest intrasession reproducibility values were 0.630 for invasive SCC at 128 kHz, 0.444 for SCC in situ at 16 kHz, and 0.460 for SK at 128 kHz. Electrical impedance dermography modeling revealed significant differences between SCC and inflamed SK in normal skin (P < 0.001) and also between invasive SCC and SCC in situ (P

Background/Aims: T-cell acute lymphoblastic leukemia (T-ALL) is an uncommon, aggressive malignancy that rarely presents in the skin and is generally not considered as part of the differential diagnosis by dermatologists and dermatopathologists. We describe an unusual case of T-ALL presenting with folliculocentric, erythematous papules on the face, histologically resembling mycosis fungoides (MF). Immunostaining for terminal deoxynucleotidyl transferase (TdT) was positive in tumor cells, supporting the diagnosis of cutaneous involvement by T-ALL. TdT is a nuclear enzyme expressed by immature lymphoid malignancies, but the expression pattern of this marker is not well characterized in the skin. We aimed to assess TdT staining in skin biopsies with similar-appearing lymphocytic infiltrates. Methods: We evaluated the immunostaining profile of TdT in a cohort of 23 patients, including 13 cases of MF and 10 cases of spongiotic dermatitis. Results: The lymphocytes in the MF and spongiotic dermatitis cases lacked nuclear staining for TdT. Nonspecific, granular, cytoplasmic staining was observed in a small number of background cells. Conclusions: TdT may assist dermatopathologists in discriminating malignant infiltrates of T-ALL from other conditions.

Potential anti-inflammatory and anticarcinogenic effects of aspirin (ASA) may be suitable for melanoma chemoprevention, but defining biomarkers in relevant target tissues is prerequisite to performing randomized controlled chemoprevention trials. We conducted open-label studies with ASA in 53 human subjects with melanocytic nevi at increased risk for melanoma. In a pilot study, 12 subjects received a single dose (325 mg) of ASA; metabolites salicylate, salicylurate, and gentisic acid were detected in plasma after 4−8 h, and prostaglandin E2 (PGE2) was suppressed in both plasma and nevi for up to 24 h. Subsequently, 41 subjects received either 325 or 81 mg ASA (nonrandomized) daily for one week. ASA metabolites were consistently detected in plasma and nevi, and PGE2 levels were significantly reduced in both plasma and nevi. Subchronic ASA dosing did not affect 5” adenosine monophosphate-activated protein kinase (AMPK) activation in nevi or leukocyte subsets in peripheral blood, although metabolomic and cytokine profiling of plasma revealed significant decreases in various (non-ASA-derived) metabolites and inflammatory cytokines. In summary, short courses of daily ASA reduce plasma and nevus PGE2 and some metabolites and cytokines in plasma of human subjects at increased risk for melanoma. PGE2 may be a useful biomarker in blood and nevi for prospective melanoma chemoprevention studies with ASA.

Little information is available as to the potential role of HER-2 as a therapeutic target in colon cancers, which express much fewer HER-2 receptors than breast cancer cells. Treatment of certain human colon cancer cell lines with the HER-2 inhibitory antibody mAb 4D5 demonstrated a role for HER-2 in mediating proliferation, apoptosis and tumorigenicity. However, only the cell lines that were dependent on autocrine EGFR-mediated cell proliferation were susceptible to the antiproliferative and antitumorigenic effects of HER-2 inhibition. The relative levels of HER-2, EGFR, HER-3 and HER-4 were not predictive of responsiveness to mAb 4D5. Treatment with HER-2 antibodies caused a decrease in HER-2 protein levels in all of the colon cancer cell lines and also significantly decreased EGFR levels but only in the EGFR-dependent cell lines. Treatment with mAb 4D5 caused the rapid ubiquitination and ligand-dependent downregulation of the EGFR in an EGFR-dependent colon cancer cell line. Treatment of athymic mice engrafted with EGFR-dependent colon cancer cells with mAb 4D5 caused tumor regression and a decrease in EGFR tyrosine phosphorylation in the tumor cells. EGFR-independent colon cancer cell xenografts were resistant to mAb 4D5 therapy. Combined inhibition of HER-2 and EGFR caused large areas of necrosis in EGFR-dependent colon cancer xenografts, suggesting a benefit of combined HER-2 and EGFR inhibitor therapy. Predicting clinical responsiveness of human colon cancer cells to anti-HER-2 and anti-EGFR therapy may require demonstration of EGFR tyrosine kinase dependency of the cells. © 2003 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Southern right whales (SRWs, Eubalena australis) are polymorphic for an X-linked pigmentation pattern known as grey morphism. Most SRWs have completely black skin with white patches on their bellies and occasionally on their backs; these patches remain white as the whale ages. Grey morphs (previously referred to as partial albinos) appear mostly white at birth, with a splattering of rounded black marks; but as the whales age, the white skin gradually changes to a brownish grey color. The cellular and developmental bases of grey morphism are not understood. Here we describe cellular and ultrastructural features of grey-morph skin in relation to that of normal, wild-type skin. Melanocytes were identified histologically and counted, and melanosomes were measured using transmission electron microscopy. Grey-morph skin had fewer melanocytes when compared to wild-type skin, suggesting reduced melanocyte survival, migration, or proliferation in these whales. Grey-morph melanocytes had smaller melanosomes relative to wild-type skin, normal transport of melanosomes to surrounding keratinocytes, and normal localization of melanin granules above the keratinocyte nuclei. These findings indicate that SRW grey-morph pigmentation patterns are caused by reduced numbers of melanocytes in the skin, as well as by reduced amounts of melanin production and/or reduced sizes of mature melanosomes. Grey morphism is distinct from piebaldism and albinism found in other species, which are genetic pigmentation conditions resulting from the local absence of melanocytes, or the inability to synthesize melanin, respectively.