Eruptive Multifocal Cutaneous Mucinous Cysts.

Cutaneous cysts lined by mucinous epithelium are rare entities. We report an unusual case of a 60-year-old female patient who presented with a 2-month history of eruptive cystic papules on her right thigh. Histopathologic study showed multiple, multiloculated cysts located in the dermis lined by nonciliated mucinous epithelium. The cyst lining was positive for AE1/AE3, CK7, CK20, and GCDFP15. Patchy positivity was noted on the p53 stain. Attenuated Sox10 positive cells were identified, raising the possibility of sweat duct origin; however, no myoepithelial layer was identified by p63 staining. Mullerian markers, including ER, PR, WT1, and Pax8, were negative. We propose this as a unique case that may represent mucinous metaplasia of a cystic sweat duct lesion. Here, we review the literature of mucinous and other glandular cutaneous cysts.

Chromosomal anomalies in primary cutaneous follicle center cell lymphoma do not portend a poor prognosis.

BACKGROUND: The t(14;18)(q32;q21) chromosomal translocation is found in the majority of nodal follicular lymphomas but only rarely in primary cutaneous follicle center cell lymphomas (PCFCL). Recent studies have postulated that the translocation is more prevalent in PCFCL than previously described and that it might be a molecular prognostic marker. OBJECTIVES: The purpose of our study was to analyze cases of PCFCL for the presence of a t(14;18) translocation using fluorescence in situ hybridization to detect balanced translocations involving either the BCL2 or MALT1 loci and to correlate the results with growth pattern, immunophenotype, and clinical outcome. METHOD: In all, 57 patients with PCFCL were extracted from our cutaneous lymphoma database. Retrospective analysis of clinical parameters including lesion type, location, diagnostic stage, lactate dehydrogenase, initial treatment, relapse rate, and survival was performed. RESULTS: In all, 57 patients with PCFCL were included in this study. We detected 1 BCL2 chromosomal amplification, 4 translocations of BCL2, and 1 IGH/MALT1 translocation. LIMITATIONS: This was a case series retrospective study. CONCLUSIONS: PCFCL has an excellent 5-year overall survival (100% disease-specific survival). Chromosomal abnormalities of either BCL2 or MALT1 were detected in 10% of cases but do not correlate with a specific immune pathology or clinical outcome.

Poikilodermatous mycosis fungoides: a study of its clinicopathological, immunophenotypic, and prognostic features.

BACKGROUND: Poikilodermatous mycosis fungoides (MF) is a variant of MF, and its clinicopathological, immunophenotypic, molecular, and prognostic features have not previously been defined in the literature. OBJECTIVE: The purpose of this study was to improve the data available for this variant of MF thus enabling clinicians to apply the appropriate treatment and follow-up. METHODS: In a retrospective single center study we evaluated the clinical, histopathological, immunohistochemical, and molecular characteristics of patients with predominant (>50%) poikilodermatous lesions of MF. RESULTS: In all, 49 patients were identified. The median age at diagnosis was 44 years (15-81 years). Of 49 patients, 43 (88%) had early stage disease (≤IIA) at diagnosis. No patients had stage IV disease at presentation. A frequent association was coexistence of lymphomatoid papulosis (9/49; 18%). Histopathology review showed a high number of cases with CD8(+) CD4(-) atypical lymphocytes (38%). After diagnosis most patients were treated with expectant or skin-directed therapy. Psoralen plus ultraviolet A therapy was most frequently used and had high response rates (83%). Five (10%) of 49 received systemic therapy. The mean follow-up was 11 years, 10 months (1->40 years). In all, 47 (96%) of 49 patients had stable disease and two (4%) of 49 had progressive disease. No patients died during follow-up. LIMITATIONS: As a tertiary center our patient cohort may be expected to have more advanced and aggressive disease. CONCLUSION: Poikilodermatous MF represents a distinct clinicopathological entity from classic patch/plaque MF. It presents at a younger age and is more frequently associated with lymphomatoid papulosis. There is an increased number of cases with predominantly CD8(+) CD4(-) atypical lymphocytes. Overall there is a good response to phototherapy and the overall prognosis appears favorable.

Spiny keratoderma: case series and review.

BACKGROUND: Spiny keratoderma is a rare, possibly under-reported, condition characterized by discrete keratotic plugs arising from the palms, soles, or both. It has been associated with malignancies though there is debate as to whether spiny keratoderma is a true paraneoplastic phenomenon. It has also been linked to a variety of non-neoplastic conditions, and several cases appear to be familial. METHODS: We describe two additional cases of this rare entity and review the literature. RESULTS: Thirty-seven cases of spiny keratoderma, including ours, have been reported in the literature. Average age at presentation was 63 years. Earliest age of onset was 11 months. A variety of ethnicities were represented. Ten cases were associated with malignancies. Six cases appeared to be inherited in an autosomal dominant fashion. Several cases were reported in healthy individuals as an incidental finding though it is possible that an associated malignancy or systemic disease will declare itself with time. Treatment is generally unsatisfying with keratotic spines often recurring on cessation. Interestingly, in some patients, the spines resolve after treatment of an underlying malignancy. CONCLUSIONS: This small case series provides an opportunity to revisit the fascinating phenomena of spiny keratoderma, its possible associations, and implications for follow-up. Due to the association with cancer, all patients presenting with spiny keratoderma should undergo baseline age-appropriate malignancy screening, thence 1-2 times yearly, or as symptoms arise.

UV-A fingerprint mutations in human skin cancer.

This review of our work, presented at the Photocarcinogenesis Symposium of the 14th International Congress on Photobiology, shows that UV-A causes a similar number of gene mutations as UV-B in human skin cancer. Areas of about 20 keratinocytes from solar keratoses and squamous cell carcinomas, which are benign and malignant skin cancers, respectively, were sampled by laser capture microdissection. Automated sequencing of the p53 gene was used to detect mutations in these tumor areas, and the cause of the mutations was attributed on the basis of previously published studies. UV-A and UV-B caused similar numbers of p53 gene mutations in both benign and malignant human skin tumors, with UV-B-induced mutations being restricted to the upper areas of the tumors and UV-A-induced mutations predominating at the basal layer. Furthermore, each microdissected region within a tumor had distinct mutations showing that the skin tumors consisted of different clones of cells. This is not consistent with how human skin carcinogenesis is currently understood, and hypotheses to explain our data are presented. We propose that the UV-A waveband of sunlight is as important as UV-B in causing skin cancer in humans.

Melanogenesis: a photoprotective response to DNA damage?

Exposure to ultra violet radiation (UVR) is associated with significant long-term deleterious effects such as skin cancer. A well-recognised short-term consequence of UVR is increased skin pigmentation. Pigmentation, whether constitutive or facultative, has widely been viewed as photoprotective, largely because darkly pigmented skin is at a lower risk of photocarcinogenesis than fair skin. Research is increasingly suggesting that the relationship between pigmentation and photoprotection may be far more complex than previously assumed. For example, photoprotection against erythema and DNA damage has been shown to be independent of level of induced pigmentation in human white skin types. Growing evidence now suggests that UVR induced DNA photodamage, and its repair is one of the signals that stimulates melanogenesis and studies suggest that repeated exposure in skin type IV results in faster DNA repair in comparison to skin type II. These findings suggest that tanning may be a measure of inducible DNA repair capacity, and it is this rather than pigment per se which results in the lower incidence skin cancer observed in darker skinned individuals. This evokes the notion that epidermal pigmentation may in fact be the mammalian equivalent of a bacterial SOS response. Skin colour is one of most conspicuous ways in which humans vary yet the function of melanin remains controversial. Greater understanding of the role of pigmentation in skin is vital if one is to be able to give accurate advice to the general public about both the population at risk of skin carcinogenesis and also public perceptions of a tan as being healthy.

Survival outcomes and prognostic factors in mycosis fungoides/Sézary syndrome: validation of the revised International Society for Cutaneous Lymphomas/European Organisation for Research and Treatment of Cancer staging proposal.

PURPOSE: We have analyzed the outcome of mycosis fungoides (MF) and Sézary syndrome (SS) patients using the recent International Society for Cutaneous Lymphomas (ISCL)/European Organisation for Research and Treatment of Cancer (EORTC) revised staging proposal. PATIENTS AND METHODS: Overall survival (OS), disease-specific survival (DSS), and risk of disease progression (RDP) were calculated for a cohort of 1,502 patients using univariate and multivariate models. RESULTS: The mean age at diagnosis was 54 years, and 71% of patients presented with early-stage disease. Disease progression occurred in 34%, and 26% of patients died due to MF/SS. A significant difference in survival and progression was noted for patients with early-stage disease having patches alone (T1a/T2a) compared with those having patches and plaques (T1b/T2b). Univariate analysis established that (1) advanced skin and overall clinical stage, increased age, male sex, increased lactate dehydrogenase (LDH), and large-cell transformation were associated with reduced survival and increased RDP; (2) hypopigmented MF, MF with lymphomatoid papulosis, and poikilodermatous MF were associated with improved survival and reduced RDP; and (3) folliculotropic MF was associated with an increased RDP. Multivariate analysis established that (1) advanced skin (T) stage, the presence in peripheral blood of the tumor clone without Sézary cells (B0b), increased LDH, and folliculotropic MF were independent predictors of poor survival and increased RDP; (2) large-cell transformation and tumor distribution were independent predictors of increased RDP only; and (3) N, M, and B stages; age; male sex; and poikilodermatous MF were only significant for survival. CONCLUSION: This study has validated the recently proposed ISCL/EORTC staging system and identified new prognostic factors.

Cheilitis caused by contact allergy to cocamidopropyl betaine in '2-in-1 toothpaste and mouthwash'.

A 10-year-old girl presented with a 2-year history of severe cheilitis. Despite cessation of any lip-licking behaviour her symptoms continued to worsen, with only minimum relief from therapeutic measures. Patch testing proved strongly positive to cocamidopropyl betaine, which was noted to be present in the patient's '2-in-1 toothpaste and mouthwash'. Her cheilitis settled after avoidance of this product. Cocamidopropyl betaine, a surfactant, is a common allergen in hairdressers; however, this case highlights the importance of excluding a contact allergy to this product in patients with intractable cheilitis.

The basal layer in human squamous tumors harbors more UVA than UVB fingerprint mutations: a role for UVA in human skin carcinogenesis.

We hypothesized that a substantial portion of the mutagenic alterations produced in the basal layer of human skin by sunlight are induced by wavelengths in the UVA range. Using laser capture microdissection we examined separately basal and suprabasal keratinocytes from human skin squamous cell carcinomas and premalignant solar keratosis for both UVA- and UVB-induced adduct formation and signature mutations. We found that UVA fingerprint mutations were detectable in human skin squamous cell carcinomas and solar keratosis, mostly in the basal germinative layer, which contrasted with a predominantly suprabasal localization of UVB fingerprint mutations in these lesions. The epidermal layer bias was confirmed by immunohistochemical analyses with a superficial localization of cyclobutane thymine dimers contrasting with the localization of 8-hydroxy-2'-deoxyguanine adducts to the basal epithelial layers. If unrepaired, these adducts may lead to fixed genomic mutations. The basal location of UVA-rather than UVB-induced DNA damage suggests that longer-wavelength UVR is an important carcinogen in the stem cell compartment of the skin. Given the traditional emphasis on UVB, these results may have profound implications for future public health initiatives for skin cancer prevention.