The Perils of Skin Biopsy

Arch Dermatol. 2007 Oct;143(10):1267-71.
Wound complications following diagnostic skin biopsies in dermatology inpatients.Wahie S, Lawrence CM.
Department of Dermatology, Royal Victoria Infirmary, Queen Victoria Road, Newcastle upon Tyne NE1 4LP, England. shyamalwahie@hotmail.com

OBJECTIVES: To prospectively determine the wound complication rate for dermatology inpatients undergoing diagnostic skin biopsies during their admission and to determine significant host and procedural risk factors. DESIGN: Prospective assessment, by a single observer, of 100 postdiagnostic skin biopsy wounds in dermatology inpatients. The following data were recorded for each patient: age and sex, presence of comorbidities, smoking status, dermatologic diagnosis, use of immunosuppressive or antibiotic therapy, place of biopsy (whether in the operation theater or in the ward), grade of physician performing biopsy, biopsy site on the body, type of biopsy (whether elliptical incision, punch, shave, or curettage), and wound closure technique. MAIN OUTCOME MEASURE: Wounds were designated as having had no complication or as being complicated by infection, dehiscence, and/or hematoma. SETTING: A dedicated dermatology inpatient ward in a university teaching hospital. RESULTS: Wound complications occurred in 29 (29%) biopsies, 27 (93%) of which were the result of wound infection. Complications occurred significantly more frequently when biopsies were performed below the waist compared with above the waist (P < .02), in the ward compared with the outpatient operating theater (P < .001), in smokers compared with nonsmokers (P < .001), and in those taking corticosteroids compared with those who were not (P < .001). In addition, elliptical incisional biopsies developed complications more frequently when subcutaneous sutures were not used compared with when they had been used (P < .001).
CONCLUSIONS: This study has demonstrated a high rate of wound complications after diagnostic dermatologic surgery on dermatology inpatients with significant host and procedural risk factors. These findings are relevant for other centers with inpatient units where diagnostic biopsies are performed.

Endometriosis and risk of cutaneous melanoma

Arch Intern Med. 2007 Oct 22;167(19):2061-5.
Personal history of endometriosis and risk of cutaneous melanoma in a large prospective cohort of French women.Kvaskoff M, Mesrine S, Fournier A, Boutron-Ruault MC, Clavel-Chapelon F.Institut National de la Santé et de la Recherche Médicale, ERI 20, Institut Gustave Roussy, 39 rue Camille Desmoulins, F94805 Villejuif CEDEX, France.

BACKGROUND: An association between melanoma and endometriosis has been reported, but most findings relied on case-control studies or a limited number of melanoma cases, and therefore the available evidence is weak. Moreover, the effect of other benign gynecological diseases on melanoma risk is unknown. METHODS: We prospectively studied data from the Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale cohort, which includes 98 995 French women, insured by a national health scheme mostly covering teachers, aged 40 to 65 years at inclusion. Data on history of endometriosis and other benign gynecological diseases were regularly collected, starting in 1990. Relative risks and 95% confidence intervals were computed using Cox proportional hazards regression models. RESULTS: During 12 years of follow-up, 363 melanoma cases were ascertained among 91 965 subjects. A history of endometriosis (n = 5949) was significantly associated with a higher risk of melanoma (relative risk, 1.62; 95% confidence interval, 1.15-2.29). There was also a significantly increased risk among women with a history of fibroma (n = 24 375), compared with those who had no such history (relative risk, 1.33; 95% confidence interval, 1.06-1.67). A history of ovarian cyst, uterine polyp, breast adenoma/fibroadenoma, or breast fibrocystic disease was not significantly associated with risk.
CONCLUSIONS: These data provide the strongest evidence to date of a positive association between a history of endometriosis and melanoma risk. The association between fibroma and melanoma, which has not been previously described, warrants further investigation

Melanoma management in Victoria 1996 and 2000

This is an interesting article looking at how melanoma was managed before and after the introduction of melanoma management guidelines. It makes depressing reading. The guidelines had little effect but perhaps this was due to not enough time between issuing them and this survey. They look at biopsy type, excision margins etc. Worth reading in full HERE. It would be interesting to carry this survey out on members of the Society. Perhaps the audit can look at this.IMCC

The management of primary cutaneous melanoma in Victoria in 1996 and 2000
John W Kelly, Michael A Henderson, Vicky J Thursfield, John Slavin, Jill Ainslie and Graham G Giles
Abstract
Objective:

To describe tumour characteristics and clinical management of melanomas newly diagnosed in 1996 and in 2000 — before and after publication of the clinical practice Guidelines for the management of cutaneous melanoma by the Australian Cancer Network (1997), and their endorsement by the National Health and Medical Research Council (NHMRC) and republication (1999).
Design and setting:

Survey of clinicians involved in the management of patients with melanoma sampled from the Victorian Cancer Registry. The Registry is notified of all cases of cancer diagnosed by pathology laboratories and hospitals in both the public and private health sectors in the state of Victoria.
Patients:

People with a cutaneous melanoma newly diagnosed in 1996 and 2000. All invasive melanomas > 1.50 mm in thickness were included, and for each year random samples were selected of 100 each of invasive melanomas 0.76–1.50 mm in thickness, invasive melanomas ≤ 0.75 mm, and in-situ melanomas, plus 50 melanomas of unknown thickness.
Main outcome measures:

Biopsy method, adequacy of pathology reporting, adequacy of definitive excision (compared with margins recommended by the Guidelines), and follow-up procedures.
Results:

The use of partial biopsies increased between 1996 and 2000. Recommended margins of definitive excision were used in only 33.6% of cases. Margins were smaller than recommended for 36% of in-situ melanomas, risking recurrence of primary melanoma. Documented follow-up examinations for subsequent primary skin malignancy were uncommon (6%).
Conclusions:

Many aspects of the management of primary cutaneous melanoma appear not to meet the recommendations of the published Guidelines. Further studies to explore the reasons for failure to meet the Guideline recommendations are needed.

Multipeptide melanoma vaccines

Clinical Cancer Research 13, 6386-6395, November 1, 2007. doi: 10.1158/1078-0432.CCR-07-0486
(This article validates the use of multipeptide vaccines in melanoma vaccine research. It does not say that the technique is clinically effective. IMCC)


Immunologic and Clinical Outcomes of a Randomized Phase II Trial of Two Multipeptide Vaccines for Melanoma in the Adjuvant Setting
Craig L. Slingluff, Jr.1, Gina R. Petroni2, Kimberly A. Chianese-Bullock1, Mark E. Smolkin2, Sarah Hibbitts3, Cheryl Murphy1, Naomi Johansen1, William W. Grosh4, Galina V. Yamshchikov1, Patrice Y. Neese1, James W. Patterson5, Robyn Fink3 and Patrice K. Rehm6

Authors' Affiliations: Departments of 1 Surgery and 2 Public Health Sciences; 3 Cancer Center; and 4 Division of Hematology-Oncology, Department of Medicine; and Departments of 5 Pathology and 6 Radiology, University of Virginia, Charlottesville, Virginia

Requests for reprints: Craig L. Slingluff, Jr., Department of Surgery, Human Immune Therapy Center, University of Virginia, 1352 Jordan Hall, P.O. Box 801457, Charlottesville, VA 22908. Phone: 434-243-2611; Fax: 434-982-3276; E-mail: cls8h@virginia.edu.

Purpose: Human melanoma cells express shared antigens recognized by CD8+ T lymphocytes, the most common of which are melanocytic differentiation proteins and cancer-testis antigens. However, peptide vaccines for melanoma usually target only one or two MHC class I–associated peptide antigens. Because melanomas commonly evade immune recognition by selective antigen loss, optimization of melanoma vaccines may require development of more complex multipeptide vaccines.

Experimental Design: In a prospective randomized clinical trial, we have evaluated the safety and immunogenicity of a vaccine containing a mixture of 12 peptides from melanocytic differentiation proteins and cancer-testis antigens, designed for human leukocyte antigen types that represent 80% of the melanoma patient population. This was compared with a four-peptide vaccine with only melanocytic differentiation peptides. Immune responses were assessed in peripheral blood and in vaccine-draining lymph nodes.

Results: These data show that (a) the 12-peptide mixture is immunogenic in all treated patients; (b) immunogenicity of individual peptides is maintained despite competition with additional peptides for binding to MHC molecules; (c) a broader and more robust immune response is induced by vaccination with the more complex 12-peptide mixture; and (d) clinical outcome in this peptide vaccine trial correlates with immune responses measured in the peripheral blood lymphocytes.

Conclusions: These data support continued investigation of complex multipeptide vaccines for melanoma.

Automated dermoscopy image analysis

Can automated dermoscopy image analysis instruments provide added benefit for the dermatologist? A study comparing the results of three systems BJD Nov 2007 A. Perrinaud, O. Gaide**Department of Dermatology, University Hospital Geneva, Geneva, Switzerland, L.E. French††Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, CH-8091 Zurich, Switzerland, J.-H. Saurat**Department of Dermatology, University Hospital Geneva, Geneva, Switzerland, A.A. Marghoob‡‡Dermatology Service, Memorial Sloan-Kettering Cancer Center, New York, NY, U.S.A. and R.P. Braun*†Department of Dermatology, University Hospital Trousseau, Tours, France*Department of Dermatology, University Hospital Geneva, Geneva, SwitzerlandDepartment of Dermatology, University Hospital Trousseau, Tours, France
*Department of Dermatology, University Hospital Geneva, Geneva, Switzerland
†Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, CH-8091 Zurich, Switzerland
‡Dermatology Service, Memorial Sloan-Kettering Cancer Center, New York, NY, U.S.A.
Ralph P. Braun.
E-mail: ralph.braun@usz.ch


Summary

Background Instruments designed to provide computer program-driven diagnosis of dermoscopic images of lesions are now commercially available. Multiple publications tout the improved diagnostic accuracy of these instruments compared with that of clinicians.

Objectives Our aim was to evaluate the actual usefulness of these instruments for dermatologists practising in a pigmented lesion clinic.

Methods Over a 4-month period we subjected lesions, which were being evaluated in one of our clinics, to automated computer diagnosis performed by three commercially available instruments. We intentionally included three groups of lesions: group 1 lesions were suspicious melanocytic lesions that were scheduled to be excised; group 2 lesions were nonmelanocytic lesions; group 3 lesions were clinically obvious melanomas. The automated diagnoses provided by the instruments were compared with the dermoscopy diagnosis of experienced physicians and with histopathology.

Results We included a total of 107 lesions. One imaging system’s computer algorithm was unable to analyse one third of the lesions. All three instruments’ computer algorithms were able to identify the clinically obvious melanomas (group 3) correctly. However, all three systems tended to overdiagnose by incorrectly classifying most seborrhoeic keratoses (group 2) as potential malignant lesions. Concerning the suspect melanocytic lesions (group 1), which are precisely the lesions for which a dermatologist would welcome a second opinion, we found significant variability in the diagnostic accuracy of the instruments tested. However, all three systems providing computer-assisted diagnosis had a tendency to overdiagnose benign melanocytic lesions as potential melanomas.

Conclusions Although the image analysis systems tested by us correctly identified the clinically obvious melanomas, they were not able to discriminate between most dysplastic naevi and early malignant melanoma. Thus, for the moment these computer-assisted diagnostic imaging machines provide little to no added benefit for the experienced dermatologist/dermoscopist.

Multiple Blue Grey Dots

The significance of multiple blue-grey dots (granularity) for the dermoscopic diagnosis of melanomaBJD Nov 2007
R.P. Braun¶¶Department of Dermatology, University Hospital Zürich, Gloriastr. 31, 8032 Zürich, Switzerland, O. Gaide, M. Oliviero**Skin and Cancer Associates, Plantation, FL, U.S.A., A.W. Kopf††Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, NY, U.S.A., L.E. French, J.-H. Saurat and H.S. Rabinovitz**Skin and Cancer Associates, Plantation, FL, U.S.A.Pigmented Skin Lesion Unit, Department of Dermatology, University Hospital Geneva, 24 rue Micheli-du-Crest, CH-1211 Geneva 14, Switzerland
*Skin and Cancer Associates, Plantation, FL, U.S.A.
†Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, NY, U.S.A.
¶Department of Dermatology, University Hospital Zürich, Gloriastr. 31, 8032 Zürich, Switzerland
R.P. Braun.
E-mail: braun@melanoma.ch
Summary

Background The presence of multiple blue-grey dots (MBGD) is widely used by clinicians to decide if a pigmented lesion should be removed, but only little is known about their significance.

Objectives To evaluate the significance of MBGD for the dermoscopic diagnosis of melanoma.

Methods In part 1 we retrospectively evaluated 340 pigmented lesions for the presence and morphological appearance of granularity. One hundred and seventy melanomas were included and matched with 170 benign and dysplastic naevi which were randomly chosen from our collection. In part 2, 3773 lesions were examined prospectively in at-risk patients: all lesions with granularity were recorded, surgically removed and subjected to histopathological examination.

Results In part 1, granularity was found in 26·5% of the benign lesions and 93·5% of melanomas. The presence of granularity, granularity at the periphery, irregularly distributed granularity and granularity in association with red and white colour were statistically highly significant for the diagnosis of melanoma (P < 0·001). In part 2, granularity was found in 1·08% of the 3773 lesions and more frequently in sun-damaged skin. Sensitivity for the diagnosis of melanoma was 85% and specificity 99%.

Conclusions After the revision of many lesions with MBGD, we concluded that the term ‘granularity’ better describes this entity. Lesions with irregular granularity (periphery, irregularly distributed) should be removed especially if they are associated with red, blue or white colour. Lesions with a benign dermoscopy pattern which have granularity with a regular appearance and involving only a small portion of the lesion do not require surgical excision.

Difficult to diagnose melanomas

Melanomas That Failed Dermoscopic Detection: A Combined Clinicodermoscopic Approach for Not Missing Melanoma
Authors: PUIG, SUSANA1; ARGENZIANO, GIUSEPPE2; ZALAUDEK, IRIS; FERRARA, GERARDO3; PALOU, JOSE2; MASSI, DANIELA4; HOFMANN-WELLENHOF, RAINER5; SOYER, H. PETER5; MALVEHY, JOSEP1

Source: Dermatologic Surgery, Volume 33, Number 10, October 2007 , pp. 1262-1273(12)

Abstract:

OBJECTIVE

The objective was to describe the clinical and dermoscopic characteristics of difficult-to-diagnose melanomas (DDM). DESIGN

This study was a retrospective analysis of clinical data and dermoscopic images in a series of excised melanomas. SETTING

Cases were obtained from the database registers of three public hospitals in Barcelona (Spain), Naples (Italy), and Graz (Austria). PATIENTS

A total of 97 tumors with a main preoperative diagnosis different from melanoma and without sufficient criteria to be diagnosed clinically and dermoscopically as melanoma were studied. We studied clinical data from the patients and lesions, mean reason for excision, and consensus dermoscopic description of the lesions according to pattern analysis performed by a panel of four dermoscopists to obtain clues that allow these melanomas to be recognized. RESULTS

Ninety-three DDMs were evaluated. Three main dermoscopic categories of DDM have been identified: (1) DDMs lacking specific features (16/97), (2) DDMs simulating nonmelanocytic lesions (14/93), and (3) DDMs simulating benign melanocytic proliferations (67/93). The reasons for excision were (1) the subjective history of change referred by the patient (38% of cases), (2) the presence of clinical and/or dermoscopic “hints” for biopsy (33% of cases), and (3) the objective evidence of changes detected by digital dermoscopic follow-up (29% of cases). CONCLUSIONS
A diagnostic algorithm is proposed not to miss melanoma.

Lentigo maligna excisions

Staged excision versus Mohs micrographic surgery for lentigo maligna and lentigo maligna melanomaHobart W. Walling, MD, PhDa, Richard K. Scupham, MD, PhDb, Andrew K. Bean, MDa, Roger I. Ceilley, MDa

Background
Lentigo maligna (LM) is a relatively common tumor with increasing prevalence and substantial morbidity. A variety of treatment modalities are available, though margin-control surgery offers the highest cure rate. We were interested in comparing long-term outcomes of Mohs micrographic surgery (MMS) versus staged excision with permanent sections (SE) for treating LM or LM melanoma (LMM).

Methods
Comparative study consisting of retrospective chart review from our private practice.

Results
Fifty-seven patients (31 male, 26 female, mean age at diagnosis 69.1 ± 10.1 years) were treated in our office for LM (50) or LMM (9) between January 1986 and December 2001. Forty-one tumors (71%) were located on the head and neck. Fifty-three of the 59 tumors (90%) were primary, and 6/59 (10%) were recurrent at the time of initial treatment. Forty-one tumors (36 LM, 5 LMM) were treated with SE, and 18 (14 LM, 4 LMM) were treated with MMS. The mean preoperative lesion size (1.5 ± 0.2 cm2 for SE; 1.2 ± 0.4 cm2 for MMS), mean postoperative defect size (7.1 ± 1 cm2 for SE; 7.1 ± 1.4 cm2 for MMS), and the ratio of postoperative defect to preoperative lesion size (7.9-fold increase for SE, 11.2-fold increase for MMS) were similar between the cohorts. Mean number of stages for clear margins were similar, with 1.8 ± 0.2 stages (range: 1-7) for SE and 2.0 ± 0.2 stages (range: 1-4) for MMS; clear margins were obtained in one or two stages in 85% of cases for SE and in 67% for MMS. Three recurrences (3/41; 7.3%) occurred in the SE group while 6 recurrences (6/18; 33%) occurred in the MMS group (P < .025). The mean follow-up duration was 95 months (range: 60-240) in the SE group and 117.5 months (range: 61-157) in the MMS group.

Limitations
Results are limited to a single practice site and fewer patients underwent MMS compared to SE. Patients were not randomized as cases were ascertained retrospectively.

Conclusion
Staged excision of LM and LMM is associated with a significantly lower recurrence rate with no difference in surgical defect size compared to MMS. To our knowledge, this is the first study directly comparing these two surgical techniques for managing this form of melanoma. Our extended follow-up duration exceeds that of most previous reports.

What predicts severe histological dysplasia/early melanoma in excised atypical melanocytic lesions

For me this is a useless study that probably would not apply in Australia. They apparently did not use dermatoscopy to assess the degree of atypia but only looked at clinical factors. The older you are the more likely the excised pigmented lesion is to show atypia. Marvellous!

A retrospective study addressed to understanding what predicts severe histological dysplasia/early melanoma in excised atypical melanocytic lesions.Strauss RM, Elliott F, Affleck P, Boon AP, Newton-Bishop JA.
Department of Dermatology, Leeds General Infirmary and St James’s University Hospital, Leeds LS9 7TF, U.K.

Background Atypical naevi are common benign skin lesions but are also recognized both as precursors of and risk factors for melanoma. It is therefore imperative to excise those lesions that are either likely to progress or are already progressing to melanoma. Clinically, however, it may be difficult to distinguish these from benign atypical naevi with bland histology. Objectives To analyse the clinical characteristics of excised melanocytic lesions and to identify the predictors of severe histological atypia/melanoma in situ and invasive melanoma. Methods The case notes of 434 patients who had melanocytic lesions removed at a pigmented lesion clinic were studied retrospectively. A single pathologist reviewed the excised lesions and clinical characteristics predictive of malignancy were identified. Results The best predictors of melanoma were older age, history of change and site on an extremity, but only older age was predictive of severe histological atypia/melanoma in situ as opposed to mild to moderate atypical histology. Conclusions These results confirm the difficulty of differentiating accurately between benign atypical naevi and borderline lesions or early melanoma in a clinical setting. It is therefore necessary to have a sufficiently low threshold for excision to avoid missing early melanomas, particularly in older patients presenting with lesions on the extremities.

NM23 protein in primary cutaneous melanoma

This is an interesting article with a presumably simple test that inversely correlates with adverse prognostic factors in melanoma.

Dermatopathological indicators of poor melanoma prognosis are significantly inversely correlated with the expression of NM23 protein in primary cutaneous melanoma
Authors: Ferrari, Donata; Lombardi, Mara1; Ricci, Roberto2; Michiara, Maria3; Santini, Marcello1; De Panfilis, Giuseppe1

Source: Journal of Cutaneous Pathology, Volume 34, Number 9, September 2007 , pp. 705-712(8)
Abstract:

Background: 

Some dermatopathological parameters are recognized as dominant indicators of high metastatic potential in melanoma, especially Breslow thickness, ulceration, Clark's level of invasion and mitotic rate. Because NM23 protein is the product of a melanoma metastasis suppressor gene, the aim of this study was to compare such dermatopathological indicators of melanoma prognosis with NM23 protein expression in primary cutaneous melanoma. Methods: 

The immunohistochemical NM23 expression was semiquantitatively assessed in 30 primary cutaneous melanomas. Ten dermatopathological parameters were evaluated and compared with NM23 expression. Results: 

A significant inverse correlation was found for NM23 expression in comparison with Breslow thickness (p < 0.01), ulceration (p < 0.05), Clark's level (p < 0.01), mitotic rate (p < 0.05), and vertical growth phase (p < 0.05). By contrast, no significant correlation was found for NM23 expression in comparison with cell morphology, presence of adjacent nevus, pigmentation, tumor-infiltrating lymphocytes, and regression was impossible to evaluate.
Conclusions: 

The expression of NM23 protein in primary cutaneous melanoma is significantly inversely correlated with dermatopathological parameters currently recognized as powerful indicators of melanoma prognosis. NM23 may be therefore considered in the dermatopathological evaluation of primary cutaneous melanoma.

Dermatoscopy of Dermatofibromas

Conventional and Polarized Dermoscopy Features of Dermatofibroma
Anna Liza C. Agero, MD; Salvatore Taliercio; Stephen W. Dusza, MPH; Cristina Salaro, MD; Paul Chu, MD; Ashfaq A. Marghoob, MD


Arch Dermatol. 2006;142:1431-1437.

Objective To evaluate dermoscopic features and patterns of dermatofibromas using conventional and polarized light dermoscopy.

Design Dermatofibromas were imaged using conventional nonpolarized contact dermoscopy (NPD), polarized contact dermoscopy (PCD), and polarized noncontact dermoscopy, followed by evaluation and comparison of dermoscopic features of the lesions.

Setting Dermatology clinic specializing in pigmented lesions.

Patients Fifty patients with dermatofibromas.

Results The most common features of dermatofibromas observed with NPD and PCD were central white scarlike patches (37 [74%] and 42 [84%], respectively), brown globulelike structures (21 [42%] and 22 [44%]), vascular structures (24 [48%] and 22 [44%]), and a peripheral fine pigmented network (36 [72%] for both). A newly described feature observed with PCD was a central white patch characterized by shiny white streaks. With polarized noncontact dermoscopy, the most characteristic feature was a central pink hue or "vascular blush" (44 [88%]) and visibility of blood vessels (41 [82%]). The most common pattern identified with NPD and PCD was the combination of a peripheral pigmented network and a central white patch in 28 (56%) and 31 (62%) of lesions, respectively. With polarized noncontact dermoscopy, the most common pattern was a central pink hue with a peripheral pigmented network (23 [46%]). There was good to excellent agreement when comparing NPD with PCD images, but there was a variable level of agreement when polarized noncontact dermoscopy images were compared with NPD and PCD images.

Conclusions Conventional and polarized light dermoscopy are not equivalent but may be complementary. This study highlights some salient differences. We were able to identify new dermoscopic features and patterns not previously described with conventional dermoscopy. These new criteria can aid in the diagnosis of dermatofibroma.


Author Affiliations: Dermatology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York (Drs Agero, Salaro, and Marghoob and Mr Dusza); Albany Medical College, Albany (Mr Taliercio); and Pathology Associates, Port Chester (Dr Chu), NY.







THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES


Differences Between Polarized Light Dermoscopy and Immersion Contact Dermoscopy for the Evaluation of Skin Lesions
Benvenuto-Andrade et al.
Arch Dermatol 2007;143:329-338.
ABSTRACT | FULL TEXT

Combined malignant melanoma and basal cell carcinoma

J Cutan Pathol. 2007 Sep;34(9):731-5. Links
Combined malignant melanoma and basal cell carcinoma tumor of the intermingled type.Braun-Falco M.
Department of Dermatology, University Medical Center Freiburg, Freiburg, Germany.

Background: The combination of malignant melanoma (MM) and basal cell carcinoma (BCC) within a single tumor is an unusual finding. Case report: An 84-year-old white man with a pigmented tumor on the back showing a combination of MM and BCC. Results: A 1.5 x 1.5-cm irregular brown lesion on the back was clinically suggestive of MM. Histopathologically, the lesions turned out to be a combined tumor consisting of a superficial BCC and a regressive MM with a tumor thickness of 1.25 mm. The conglomerates of the BCC lay within the MM and were admixed with a high number of Melan-A-positive melanocytic cells. Conclusion: By reviewing the low number of published cases, we found that a combined MM-BCC tumor exists in two variants: a collision type in which components of each cell type are clearly demarcated and an intermingled type in which both cell types grow intimately together. Although both types occur as a mere incidence, in particular, the intermingled type may be diagnostically challenging and the evaluation of its dignity may be questionable.

Search on this topic in PubMed

Malignant melanoma of the anal region

Malignant melanoma of the anal region
Authors: Heyn, J.; Placzek, M.1; Ozimek, A.; Baumgaertner, A. K.2; Siebeck, M.; Volkenandt, M.1

Source: Clinical & Experimental Dermatology, Volume 32, Number 5, September 2007 , pp. 603-607(5)

Publisher: Blackwell Publishing
Abstract:

Summary

Malignant melanoma (MM) of the anal region is an uncommon disease. In many cases, the disease is undetected or mistaken for a benign polyp or haemorrhoids until it reaches an advanced state. Owing to delayed diagnosis and early metastases, the prognosis is often poor. In contrast to melanomas of the skin, a history of sun exposure does not seem to have an impact in development of MM in this region. Anorectal melanomas (AM) are most common in the rectum, followed by the anal canal and anal verge. Ras mutations, especially in codon 61 of the N-ras oncogene, are common in CM and rare in melanomas of the vulva and anorectum. The diagnosis of an AM is usually made using a biopsy. Histopathological examinations show spindle-shaped and pleomorphic cells. Adjuvant immunohistological markers are the calcium-binding protein S-100, the melanoma antigen HMB-45, the melanoma-expressed protein Melan A, and microphthalmia-associated transcription factor (MiTF). To date, there are few published guidelines for the correct management of AM, and surgery remains the mainstay of treatment. We report on a 39-year old man who presented with a 5-week history of recurrent prolapse of an anal tumour. The tumour was histologically confirmed to be malignant melanoma.

How Does Inflammation Cause Skin Cancers?

How Does Inflammation Cause Skin Cancers?
Observations and controlled animal studies suggest that chronic inflammation induces SCCs; we may now know a bit more about how.

Chemokines are cytokines that attract lymphocytes. In skin, the CC class of chemokines may be especially important. Antigen-experienced T cells express CC-type receptors (CCRs); indeed, CCR4 mediates homing of cutaneous T cells. A novel chemokine receptor, D6, soaks up these CC chemokines and, in normal circumstances, helps shut off inflammation by making the chemokines unavailable.

Now, a group of researchers reports that D6-deficient mice show greatly increased susceptibility to developing papillomas induced by the inflammation-producing carcinogen phorbol ester. In contrast, transgenic mice with lots of D6 are resistant to tumor formation. Without D6 receptors, CC chemokine ligand-3 (CCL3) continues to attract aberrantly (in excess, and for a longer time) CD3+ T cells and dermal mast cells.

Comment: Infiltration of CD3+ T cells and dermal mast cells has previously been associated with development of skin cancer. The resultant excess in cytokines and cells leads to epidermal hyperproliferation and ras-driven tumor formation. The chronic presence of T cells and mast cells and persisting inflammation also increase the tendency for squamous cell carcinomas to invade and metastasize.

Chronic inflammation in human oral mucosa — from tobacco carcinogens, human papillomavirus, or chronic allergic stomatitis — may cause chronic overproduction of CC chemokines. Perhaps these abundant CC chemokines saturate all D6 receptors, allowing the overflow to bind to active CCRs and induce cancers. Many SCCs of the oral mucosa are driven by ras mutations, so ras-driven proliferation of squamous cells by chemokines has potential clinical relevance, including for possible interventions. Most SCCs in skin are based on mutations of p53 rather than ras. We don’t know yet if excessive tissue chemokine levels foster gain-of-function mutations of p53.

— Mark V. Dahl, MD

Eccrine Porocarcinoma

Eccrine porocarcinoma: Clinical and pathological studies of 12 cases Authors: SHIOHARA, Junko; KOGA, Hiroshi; UHARA, Hisashi; TAKATA, Minoru; SAIDA, Toshiaki

Source: Journal of Dermatology, Volume 34, Number 8, August 2007 , pp. 516-522(7)

Publisher: Blackwell


Abstract:


Twelve cases of eccrine porocarcinoma have been reported at our facility in the past 10 years. All of them were Japanese; half had lymph node metastases; and one-third died of this disease. Lymph node metastasis was correlated with pathological lymphovascular invasion. Death was correlated with a pathological growth pattern and clinical lymph node metastasis. Sentinel lymph node biopsy was performed usefully in two patients.

Seb K to Lichenoid keratosis

Dermoscopic pattern of intermediate stage in seborrhoeic keratosis regressing to lichenoid keratosis: report of 24 casesP. Zaballos, S. Blazquez**Pathology, Hospital de Sant Pau i Santa Tecla, 43004 Tarragona, Spain, S. Puig††Melanoma Unit, Dermatology Department, Hospital Clinic, IDIBAPS, Barcelona, Spain, E. Salsench, J. Rodero, J.M. Vives and J. Malvehy††Melanoma Unit, Dermatology Department, Hospital Clinic, IDIBAPS, Barcelona, SpainDepartments of Dermatology and *Pathology, Hospital de Sant Pau i Santa Tecla, 43004 Tarragona, Spain
†Melanoma Unit, Dermatology Department, Hospital Clinic, IDIBAPS, Barcelona, Spain
Pedro Zaballos Diego.
E-mail: PZaballos@aedv.es
Conflicts of interest
None declared.

Summary

Background Lichenoid keratosis (LK) is a well-described entity which has been proposed to represent an immunological or regressive response to pre-existing epidermal lesions such as solar lentigines or seborrhoeic keratoses.

Objectives To evaluate the dermoscopic criteria of a series of cases of LK with remaining areas of seborrhoeic keratosis which were both dermoscopically and histologically diagnosed.

Methods Pigmented lesions with dermoscopic areas of seborrhoeic keratosis and LK in the same tumour were consecutively diagnosed and prospectively included in the study. All pigmented lesions were examined and registered using DermLite Foto equipment (3Gen, LLC, Dana Point, CA, U.S.A.), at 10-fold magnification, at the Dermatology Department of Hospital de Sant Pau i Santa Tecla (Tarragona, Spain), between 1 January 2003 and 31 December 2005.

Results In total, 24 cases of lesions with dermoscopic areas of seborrhoeic keratosis and LK were collected. In four lesions (17%), the clinical differential diagnosis without dermoscopy included malignant melanoma and in seven lesions (29%), basal cell carcinoma. The diagnosis of LK was clinically considered without dermoscopy in only six cases (25%). A granular pattern was observed to be distributed throughout the LK areas of the lesions. This pattern consisted of the presence of brownish-grey, bluish-grey or whitish-grey coarse granules that formed, in 11 cases (46%), globules and/or short lines. In one lesion, located on the face, these short lines produced annular or rhomboid structures as seen in lentigo maligna melanoma.

Conclusions Dermoscopy is a useful tool which assists in the correct clinical recognition of LK, which may also potentially illuminate the pathogenesis of these tumours, showing the intermediate stage of regressing epidermal lesions in an LK.

Papilloma virus and Actinic Keratoses

This study was interesting looking at the potentiation of the developement of actinic keratoses in patients who had associated papilloma virus. Can the study on SCC incidence be far behind? IMCC

Sun-Related Factors, Betapapillomavirus, and Actinic Keratoses
A Prospective Study

Penelope McBride, MBBS, MPhil; Rachel Neale, BVSc, PhD; Nirmala Pandeya, BSc, MMedSc; Adèle Green, MBBS, PhD


Arch Dermatol. 2007;143:862-868.

Objective To examine prospectively the relationship among sun exposure, Betapapillomavirus, and development of actinic keratoses.

Design Prospective, community-based cohort study.

Setting Township of Nambour in Southeast Queensland, Australia.

Participants A total of 291 randomly selected adults aged 36 to 86 years with the presence or absence of Betapapillomavirus DNA in eyebrow hair follicle cells known at baseline in August 1996 and with subsequently documented sun exposure histories.

Main Outcome Measures Prevalence of actinic keratoses in March 2003 after 7 years of follow-up.

Results Beyond the known determinants of multiple actinic keratoses, namely, advanced age, male sex, fair skin, and lifetime occupational sun exposure, Betapapillomavirus infection was associated with having more than 10 actinic keratoses (odds ratio, 1.8; 95% confidence interval, 0.7-4.4). However, Betapapillomavirus positivity led to a significant 13-fold increase in the risk of actinic keratoses among those 60 years or older, a nearly 6-fold increase in risk when combined with fair skin color, and a doubling in risk of actinic keratoses when combined with high sun exposure, recent or cumulative, compared with those who had neither Betapapillomavirus infection nor the respective risk factor of interest.

Conclusions Although the presence of Betapapillomavirus DNA in eyebrow hair follicle cells had only a small independent association with actinic keratoses, Betapapillomavirus infection in combination with key risk factors increased the risk of actinic keratoses, which is consistent with a potentiation by Betapapillomavirus of the effect of established causal factors.

Diagnosing Melanoma in Qld.

This study up to the end of 2003 indicates the rising importance of skin cancer clinics in early diagnosis of melanoma in Queensland. That role has probably massively increased since then. Does anyone know if the thickness at diagnosis of melanoma in rural Qld is markedly different from the cities? IMCC

Clinical pathways to diagnose melanoma: a population-based study.

ORIGINAL ARTICLES

Melanoma Research. 17(4):243-249, August 2007.
Baade, Peter D.; Youl, Philippa H.; English, Dallas R.; Mark Elwood, J.; Aitken, Joanne F.
Abstract:
To better understand the clinical diagnostic process for invasive melanoma in Queensland. Descriptive population-based study of Queensland residents (n=3772) aged 20-75 years diagnosed with invasive melanoma between January 2000 and December 2003. Information was obtained via telephone interview combined with pathology data from the Queensland Cancer Registry. About 85% of melanoma patients diagnosed in Queensland saw a general practitioner at least once during the process, most of these for the initial consultation. Almost one-fifth of patients (18.1%) saw a skin clinic doctor sometime through the diagnosis pathway; this proportion increased significantly over the study period (P<0.001). The most common pathway for diagnosing melanoma was an initial consultation by a general practitioner followed by referral to a surgeon for a definitive diagnosis. People living in southeast Queensland were more likely to see a dermatologist compared with those living in more rural or remote areas (14.7 versus 6.8%), more likely to see a skin clinic doctor (21.8 versus 7.2%), or a surgeon (54.9 versus 49.3%) at least once during the diagnostic process, and less likely to see a general practitioner (76.8 versus 90.2%). This descriptive study has demonstrated the complexity and diversity of clinical diagnostic pathways for melanoma in Queensland, highlighting the important role of general practitioners and the emerging role of primary care skin clinics. Although this system has resulted in a very favourable thickness distribution for diagnosed melanomas, access issues for people living in rural and remote areas of Queensland need to be addressed.

Subungual melanoma

Thumb subungual melanoma: Is amputation necessary?
Sukh S. Rayatt, a, , Anne L. Danceya and Paul M. Davisona
aDepartment of Plastic and Reconstructive Surgery, University Hospital of North Staffordshire, Stoke City Hospital, Stoke-on-Trent ST4 6QG, UK
Summary

Subungual melanoma is uncommon. Traditional teaching advocates amputation of the affected digit. Recent studies have shown that more distal levels of amputations do not compromise survival or recurrence rates. When the thumb is involved, functional and aesthetic loss can be substantial. We present a new conservative, digit-sparing approach in the treatment of subungual melanoma of the thumb. Four informed patients were recruited to undergo the new treatment. Local excision with 1 cm margins down to and including the periosteum was carried out. Reconstruction was with a local flap. There has been one recurrence and no deaths with a minimum of 6 years follow up. In selected cases, conservative management of subungual melanoma allows preservation of length and minimises disability.

PDT and Actinic Cheilitis

The Efficacy of Photodynamic Therapy in Actinic Cheilitis of the Lower Lip: A Prospective Study of 15 Patients
Authors: BERKING, CAROLA1; HERZINGER, THOMAS1; FLAIG, MICHAEL J.1; BRENNER, MICHAELA1; BORELLI, CLAUDIA1; DEGITZ, KLAUS1

Source: Dermatologic Surgery, Volume 33, Number 7, July 2007 , pp. 825-830(6)

Abstract:

BACKGROUND

Photodynamic therapy (PDT) has been developed into a widely used method to treat actinic keratoses and basal cell carcinoma. OBJECTIVE

The objective was to assess the efficacy of PDT in the treatment of actinic cheilitis of the lower lip. METHODS

In this prospective, uncontrolled study at a university dermatology department, 15 patients with actinic cheilitis received two sessions of PDT of the lower lip at an interval of 1 week using methylaminoxopentanoate and red light. Clinical and histopathologic evaluation was performed 3 months after therapy. RESULTS

Complete clinical cure was observed in 47% (7/15) and partial cure in another 47% (7/15) of the patients. By histopathologic analysis, residual disease was found in 62% (8/13). Cosmetic results and patients' satisfaction were good to excellent in most cases. Local pain was sufficiently controlled by local anesthesia. CONCLUSION

PDT can be an effective noninvasive method to treat actinic cheilitis of the lower lip.

Metvix and BCC margins on the face

Unfortunately in the Summary we are not told the histological nature of the BCCs on the face. It is the infiltrative and morphoeic lesions we are most interested in as they are the most difficult to accurately define.IMCC

Photodetection of basal cell carcinoma using methyl 5-aminolaevulinate-induced protoporphyrin IX based on fluorescence image analysis
Authors: Won, Y.1; Hong, S. H.1; Yu, H. Y.2; Kwon, Y. H.; Yun, S. J.; Lee, S. C.; Lee, J. B.

Source: Clinical & Experimental Dermatology, Volume 32, Number 4, July 2007 , pp. 423-429(7)

Publisher: Blackwell Publishing

Abstract:

Summary Background. 

The preferential accumulation of 5-aminolaevulinic acid (ALA)-induced protoporphyrin IX (PpIX) in neoplastic cells supports its potential use in the photodetection of porphyrin fluorescence in tumour cells. Hence, epithelial tumours, including basal cell carcinoma (BCC), might be visualized using the fluorescence of selectively accumulated ALA-induced PpIX. Aim. 

In this study, we evaluated the clinical efficacy of PpIX fluorescence images using fluorescence image analysis (FIA) to define the lateral border between the tumour and tumour-free areas of facial BCC. Methods. 

FIA was used to define the lateral border between the tumour and tumour-free areas on red fluorescence images induced by the topical application of methyl 5-aminolaevulinate (MAL) ointment. According to the FIA results, 50 tissue samples, obtained from 10 patients with BCC, were divided into three categories: tumour area (n = 10), suspected tumour area (n = 20) and suspected tumour-free area (n = 20). These tissue samples were evaluated by histopathological examination. The FIA tool marked out the PpIX fluorescence image for defining the lateral border between the BCC tumour and tumour-free areas. Results. 

The rate of tumour detection from BCC lesions using PpIX fluorescence with the FIA tool showed a sensitivity of 94.1% and specificity of 82.6%. Conclusion. 

These results suggest that MAL-induced PpIX fluorescence imaging using FIA is quite sensitive and specific for detecting tumour and occult tumour in facial BCC lesions. This method of presurgical in vivo imaging is therefore proposed as a useful tool for defining the lateral border between BCC tumour and tumour-free areas

SCC and the Medical Oncologist

This editorial looked at ways in which medical oncologists could become involved earlier in the management of aggressive SCCs of the skin. It comments on a paper in that issue of the journal which looked at using oral retinoids combined with Interferon injections 3 times a week with patients with severe aggressive or recurrent SCCs. Unfortunately they did no better than controls
The editorial is a useful summary. It can be viewed here
Randomized Trial of Adjuvant 13-cis-Retinoic Acid and Interferon Alfa for Patients With Aggressive Skin Squamous Cell CarcinomaAbenaa M. Brewster, J. Jack Lee, Gary L. Clayman, John L. Clifford, Mary Jo T. Necesito Reyes, Xian Zhou, Anita L. Sabichi, Sara S. Strom, Robert Collins, Christina A. Meyers, Scott M. Lippman

From the Departments of Clinical Cancer Prevention, Biostatistic and Applied Mathematics, Head and Neck Surgery, Thoracic/Head and Neck Medical Oncology, Epidemiology and Neuro-oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX; and the Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center and Feist-Weiller Cancer Center, Shreveport, LA

Address reprint requests to Scott M. Lippman, MD, Department of Thoracic and Head and Neck Medical Oncology, Unit 432, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77230-1439; e-mail: slippman@mdanderson.org

Purpose: To conduct a phase III trial of adjuvant 13-cis-retinoic acid (13cRA) plus interferon alfa (IFN-) for preventing tumor recurrence and second primary tumors (SPTs) of skin squamous cell carcinoma (SCC) among patients with aggressive skin SCC.

Patients and Methods: Sixty-six patients with aggressive skin SCC were randomly assigned to receive either 6 months of combined 13cRA (1 mg/kg/d orally) and IFN- (3 x 106 U subcutaneously three times per week) or no adjuvant therapy (control group) after SCC surgery and/or radiation.

Results: At 21.5 months median follow-up, treatment did not improve the time to tumor recurrence and SPT versus control (hazard ratio [HR], 1.13; 95% CI, 0.53 to 2.41), time to tumor recurrence (HR, 1.08; 95% CI, 0.43 to 2.72), or time to SPT (HR, 0.89; 95% CI, 0.27 to 2.93). Adjuvant 13cRA and IFN- was moderately tolerable; 29% of patients in the treatment arm required dose reductions for grade 3 or 4 toxicities.

Conclusion: Results of this phase III trial do not support 13cRA plus IFN- for adjuvant therapy of aggressive skin SCC. With high rates of tumor recurrence and SPTs, patients with aggressive skin SCC continue to have an unmet medical need, with devastating mortality, morbidity, and financial consequences. Promising agents with preclinical and early clinical results relevant to aggressive skin SCC deserve a high priority for future clinical drug development.

Margins for Dermatofibrosarcoma Protuberans

This article describes a prospective study of margins and number of attempts to achieve those margins in a group of patients with dermatofibrosarcoma protuberans.
Microscopic Margins and Results of Surgery for Dermatofibrosarcoma Protuberans.

RECONSTRUCTIVE

Plastic & Reconstructive Surgery. 119(6):1779-1784, May 2007.
Popov, Pentscho M.D.; Bohling, Tom M.D., Ph.D.; Asko-Seljavaara, Sirpa M.D., Ph.D.; Tukiainen, Erkki M.D., Ph.D.
Abstract:
Background: Dermatofibrosarcoma protuberans is a rare low-grade sarcoma of the skin with a tendency to recur locally after inadequate excision. Treatment has traditionally been wide excision with a 2- to 3-cm gross margin. Because of the variable results presented in mainly retrospective reports, it has been queried whether local control can be as good with conventional surgery as with micrographic surgery.

Methods: Forty patients with dermatofibrosarcoma protuberans treated by surgical excision were operated on at our center from 1987 to 2001. Data were recorded prospectively. Twenty-seven patients presented with a primary tumor and 13 with a locally recurrent tumor primarily operated on elsewhere. Gross and histologic margins were studied in detail.

Results: At a mean follow-up of 40 months, there were no recurrences. Thirty-four patients required single, five patients two, and one patient three operations before the margins were adequate (mean, 1.2 stages per patient). Twenty-three patients (58 percent) needed reconstructions. Tumor-free margins were obtained in 39 patients. The average thickness of surgical gross margins was 3.1 cm; histologically defined margins averaged 1.6 cm.

Conclusions: Good local control can be achieved with wide surgery. Histologic tumor-free margins differ greatly from gross margins and are difficult to assess clinically and macroscopically. Careful postoperative histologic examination with margins measured in millimeters should be carried out to define the adequacy of excision in all directions. On average, a 1.6-cm histologic margin was adequate for complete local control. Most patients can be operated on in one stage. Reconstructions are often needed.

Diagnostic Fluoroscopy and Skin damage

Fluoroscopy-Induced Chronic Radiation Skin Injury
A Disease Perhaps Often Overlooked Thomas H. Frazier, MD; Jeffrey B. Richardson, MD; Vilma C. Fabré, MD; Jeffrey P. Callen, MD


Arch Dermatol. 2007;143:637-640.

Background Fluoroscopy-induced chronic radiation dermatitis (FICRD) resulting from prolonged exposure to ionizing radiation during interventional procedures has been documented in the radiology and cardiology literature. However, the phenomenon has been rarely reported in the dermatologic literature. Since patients with FICRD often see a dermatologist or a primary care physician to treat their injuries, the diagnosis of FICRD is perhaps often overlooked.

Observations A 62-year-old man with type 2 diabetes mellitus and severe coronary artery disease was seen with a 2-year history of a pruritic, tender, telangiectatic patch lesion over his left scapula. Over the next 2 years, the lesion became indurated and eventually ulcerated. A skin biopsy specimen demonstrated changes consistent with a chronic radiation dermatitis. The patient was unaware of radiation exposure, but persistent questioning from his dermatologists revealed that he had undergone multiple fluoroscopy-guided cardiac procedures. This was confirmed by a review of his medical records.

Conclusion The diagnosis of FICRD should be considered for any patient who is seen with an acquired vascular lesion, a morphealike lesion, or an unexplained ulcer localized over the scapula, the back, or lateral trunk below the axilla.

Is the Siascope any value to Dermatologists for Real time melanoma screening?

Answer is not at all for this particular Dermatologist.The use of a spectrophotometric intracutaneous analysis device in the real-time diagnosis of melanoma in the setting of a melanoma screening clinicM.A. Haniffa, J.J. Lloyd**Regional Medical Physics Department, Royal Victoria Infirmary, Newcastle-upon-Tyne NE1 4LP, U.K. and C.M. LawrenceDepartment of Dermatology and *Regional Medical Physics Department, Royal Victoria Infirmary, Newcastle-upon-Tyne NE1 4LP, U.K.

Background Skin imaging devices to aid melanoma diagnosis have been developed in recent years but few have been assessed clinically.

Objectives To investigate if a spectrophotometric skin imaging device, the SIAscope, could increase a dermatologist's ability to distinguish melanoma from nonmelanoma in a melanoma screening clinic.

Methods Eight hundred and eighty-one pigmented lesions from 860 patients were prospectively assessed clinically and with the aid of the spectrophotometric device by a dermatologist. Assessment before and after spectrophotometric imaging was made and compared with histology, where available, or with the clinical diagnosis of a dermatologist with 20 years of experience.

Results One hundred and seventy-nine biopsies were performed, with 31 melanomas diagnosed. Sensitivity and specificity for melanoma diagnosis before and after spectrophotometry were 94% and 91% vs. 87% and 91%, respectively, with no significant difference in the area under the receiver operating characteristic curves (0·932 and 0·929).

Conclusions Our study provides no evidence for the use of SIAscope by dermatologists to help distinguish melanoma from benign lesions.

Chromosomal Features of Melanoma and Spitz Nevi.

This article shows the chromosomal differences between Spitz evi and Melanoma. It may be helpful in differentiating difficult histological cases some time in the future.(IMCC)
Genetic and epigenetic alterations in the differential diagnosis of malignant melanoma and spitzoid lesion
British Journal of Dermatology
Volume 156 Issue 6 Page 1287 - June 2007

M. Takata, J. Lin, S. Takayanagi, T. Suzuki**Laboratory Medicine, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto 390–8621, Japan, S. Ansai††Sapporo Institute for Dermatopathology, Sapporo, Japan, T. Kimura††Sapporo Institute for Dermatopathology, Sapporo, Japan, L. Cerroni‡‡Department of Dermatology, Medical University of Graz, Graz, Austria and T. SaidaDepartments of Dermatology and *Laboratory Medicine, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto 390–8621, Japan
†Sapporo Institute for Dermatopathology, Sapporo, Japan
‡Department of Dermatology, Medical University of Graz, Graz, Austria


Background The histopathological differentiation of malignant melanoma and Spitz naevus often presents diagnostic problems.

Objectives We aimed to find out applicable diagnostic parameters other than routine pathology.

Methods The cases included conventional melanomas and Spitz naevi as well as atypical spitzoid lesions that had posed diagnostic difficulties. We examined hotspots of mutation in the BRAF, NRAS and HRAS genes by polymerase chain reaction-based direct sequencing. We also analysed DNA copy number aberrations and the methylation of CpG sequences in several cancer-related genes by utilizing a novel methylation-specific multiplex ligation-dependent probe amplification method.

Results Twenty three of 24 conventional melanomas showed at least one of the genetic and epigenetic alterations examined, although one acral melanoma did not show any alteration. By sharp contrast, 12 Spitz naevi with an unambiguous histopathology showed no or few chromosomal aberrations, no oncogene mutations and no methylation of CpG sequences. Of the 16 ambiguous spitzoid lesions, most of which were designated atypical Spitz tumour by one of the authors, all but one showed no mutations, no methylations and few copy number aberrations. However, three tumours showed copy number loss of the cyclin-dependent kinase inhibitor 2A gene (CDKN2A), an alteration observed frequently in melanomas but not found in conventional Spitz naevi. These results show that, although most atypical Spitz tumours do not differ from conventional Spitz naevi showing virtually no genetic and epigenetic aberrations, some cases may have chromosomal aberrations that include copy number loss of the CDKN2A gene.

Conclusions Genetic and epigenetic analyses may be useful as an additional diagnostic tool to distinguish between melanoma and Spitz naevus, and may help to define subgroups in atypical Spitz tumours.

The nature of cutaneous metastases

Clinicopathologic correlation of cutaneous metastases
Sariya, D., et al. - To analyze the clinical, histopathologic, and immunohistochemical characteristics of skin metastases.
Cutaneous metastases can have variable clinical appearances and can mimic benign skin lesions. They are usually seen in patients with advanced disease, but they can be the presenting lesion. Although many metastatic adenocarcinomas can be recognized based on histologic findings alone, immunohistochemical analysis is an important diagnostic adjunct in some cases

Methodology
51 patients with biopsy-proven skin metastases and correlative clinical data.
4 dermatopathologists reviewed a random mixture of metastases and primary skin tumors.
Immunohistochemical studies for 12 markers were performed on the metastases, with skin adnexal tumors as controls.

Results
86% of the patients had known stage IV cancer, and skin metastasis was the presenting sign in 12%.
In 45% of the biopsies, the lesions were not suspected of being metastases owing to unusual clinical presentations.
76% of the patients died of disease (median survival, 5 months).
On pathologic review, many metastases from adenocarcinomas were either recognized or suspected, but the primary site was not easily identified based on histologic findings alone.
Metastases from small cell carcinomas and sarcomas were histologically misinterpreted as primary skin tumors.
Immunohistochemical analysis using a panel including p63, B72.3, calretinin, and CK5/6 differentiated metastatic carcinoma from primary skin adnexal tumors.

Why carry out Dermatoscopy?

A compilation of the discussion of this topic in the Archives and replies from Scott Menzies and Iris Zaludeck to a letter critical of their editorial can be found here

Distinguishing early melanoma histochemically.

This is an interesting paper that may point the way ahead in looking at distinguishing early melanoma from Clarke's (dysplastic) nevi. It may be useful in those more severly dysplastic histopathologically. Mind you most of us excise these fully anyway. Simply trying this test with a biopsy would not be the best thing to do!(IMCC)

Cyclooxygenase-2 (COX-2): first immunohistochemical marker distinguishing early cutaneous melanomas from benign melanocytic skin tumours.

ORIGINAL ARTICLES

Melanoma Research. 17(3):139-145, June 2007.
Chwirot, Barbara W.; Kuzbicki, Lukasz
Abstract:
We have reported recently that changes in expression level of COX-2 are correlated with development and progression of human melanoma. In this study, we investigated whether the COX-2 expression level might be a useful immunohistochemical marker for distinguishing cutaneous melanomas from benign melanocytic lesions. Up to now, immunohistochemical markers have not ensured satisfactory sensitivity and specificity of differential pathologic diagnosis of melanoma. The expression of COX-2 was determined immunohistochemically in formalin-fixed, paraffin-embedded specimens of 33 early Clark I/II melanomas and 58 naevi. Mean COX-2 expression in melanomas was significantly stronger than in naevi (P[almost equal to]10-13). A simple diagnostic algorithm using threshold values of the COX-2 expression level allows for differentiation between early melanomas and naevi with high sensitivity (Se) and specificity (Sp) (for Se between 91 and 100%, Sp values change between 96.5 and 51.7%). Areas under the receiver operating characteristic curves were, respectively, 0.97+/-0.02 and 0.86+/-0.04 for the COX-2 expression in central and border regions of the lesions. For all the melanomas (not only the early ones),the respective areas under the ROC curve values were 0.98+/-0.01 and 0.97+/-0.02. In conclusion, COX-2 is the first immunohistochemical marker that allows the distinguishing of early melanomas from benign melanocytic lesions with both high sensitivity and specificity.

Interventions for BCC

Interventions for basal cell carcinoma of the skin.Author(s): Bath-Hextall F; Perkins W; Bong J; Williams H;

BACKGROUND: Basal cell carcinoma (BCC) is the commonest skin cancer. BCCs
are slow-growing, locally invasive, epidermal skin tumours which mainly
affect white skinned people. The first line treatment is usually surgical
excision, but numerous alternatives are available. OBJECTIVES: To assess
the effects of treatments for basal cell carcinoma. SEARCH STRATEGY: We
searched the Cochrane Skin Group Specialised Register (January 2006),
the Cochrane Central Register of Controlled Trials (The Cochrane LIbrary
Issue 1, 2006), the Cochrane Database of Systematic Reviews (The Cochrane
Library Issue 1, 2006), MEDLINE (2004 to January 2006), EMBASE (2005 to
January 2006), the metaRegister of Controlled Trials (February 2006).
Cited references of all trials identified and key review articles were
searched. Pharmaceutical companies were contacted where appropriate for
reviews or unpublished trials. SELECTION CRITERIA: Inclusion criteria
were adults with one or more histologically proven, primary basal cell
carcinoma. The primary outcome measure was recurrence at three to five
years, measured clinically. The secondary outcome included early treatment
failure within six months, measured histologically. Adverse treatment
effects included aesthetic appearance and pain during and after treatment.
DATA COLLECTION AND ANALYSIS: Two authors independantly carried out study
selection and assessment of methodological quality. MAIN RESULTS: Twenty
seven studies were identified. Only one RCT of surgery versus radiotherapy
had primary outcome data at four years, showing significantly more persistent
tumours and recurrences in the radiotherapy group as compared to the surgery
group, (RR 0.09, 95%CI, 0.01 to 0.69). One study found no significant
difference for recurrence at 30 months when Moh's micrographic surgery
was compared to surgery for high risk facial BCCs, (RR 0.64, 95%CI 0.16,2.64).
One study of methylaminolevulinate photodynamic therapy (MAL PDT) versus
cryotherapy found no significant difference in recurrences in the MAL
PDT group when compared to cryotherapy at one year (RR 0.50, 95% CI 0.22,1.12).
Cryotherapy showed no significant difference in recurrences at one year
when compared to surgery on one small study. When radiotherapy was compared
to cryotherapy there were significantly fewer recurrences at one year
in the radiotherapy group compared to the cryotherapy group.Short-term
studies suggest a success rate of 87 to 88% for imiquimod in the treatment
of superficial BCC using a once-daily regimen for 6 weeks and a 76% treatment
response when treating nodular BCC for 12 weeks, when measured histologically.
AUTHORS' CONCLUSIONS: Overall there has been very little good quality
research on treatments for BCC. Most trials have only evaluated BCCs in
low risk locations. Surgery and radiotherapy appear to be the most effective
treatments with surgery showing the lowest failure rates. Although cosmetic
outcomes appear good with PDT, long term follow up data are needed. Other
treatments might have some use but few have been compared to surgery.
An ongoing study comparing imiquimod to surgery should clarify whether
imiquimod is a useful option.

Cochrane database of systematic reviews (Online: Update Software); 2007
1 1;(1)

Number of References: 63

Melanoma in Children

Melanoma in children and teenagers: an analysis of patients from the National Cancer Data Base.

Lange JR, Palis BE, Chang DC, Soong SJ, Balch CM.

Department of Surgery, Johns Hopkins Medicine, Baltimore, MD, USA jlange@jhmi.edu

PURPOSE: This study examines the demographics, presentation, and outcomes of children and teenagers with melanoma using a US hospital-based oncology database. PATIENTS AND METHODS: Data from the National Cancer Data Base from 1985 through 2003 were examined for demographics, presentation, and survival of patients aged 1 to 19 years, as well as a comparison group of patients aged 20 to 24 years. Two-sided linear and Pearson chi2 tests were calculated to examine associations. Proportions were compared using two-sided z tests. Five-year overall observed survival was evaluated using the Kaplan-Meier method and the log-rank test. Cox proportional hazards regression was used to estimate risk of mortality. RESULTS: Of 3,158 patients aged 1 to 19 years, 96.3% had cutaneous melanoma, 3.0% had ocular melanoma, and 0.7% had an unknown primary tumor. Cutaneous melanoma in patients aged 1 to 19 years was more common in girls (55.5%) and patients older than 10 years (90.5%). The demographics and presentation of cutaneous melanoma were age related; younger children were significantly more likely to be nonwhite and male and more likely to present with a head and neck primary tumors and with regional or distant metastases (linear chi2, P < .001 for sex, race, and extent of disease). Poorer survival was associated with higher stage and younger age. In contrast to patients aged 20 to 24 years, survival was not related to thickness in patients aged 1 to 19 years with localized invasive melanoma.
CONCLUSION: Melanoma in children and teenagers differs from melanoma in young adults in demographics, presentation, and survival. Further investigation is warranted to elucidate possible biologic correlates of the unique aspects of melanoma in children and teenagers.

Diet and Skin Cancer

This study from the Queensland group analysing data obtained during the Nambour study suggests that a high fat diet predisposes you to SCC but not BCC. Another explanation might be that people who eat high fat diets are not health conscious anyway and hence less likely to adopt sun safe behaviour. I have not read the whole article ,hence I do not know if they addressed this issue during their analysis of the two groups regarding their behaviour in the sun. I presume they had the same behavious or you would not have a valid study! If anyone knows Adele you might ask her.
Dietary pattern in association with squamous cell carcinoma of the skin: a prospective study
American Journal of Clinical Nutrition, Vol. 85, No. 5, 1401-1408, May 2007
Torukiri I Ibiebele, Jolieke C van der Pols, Maria Celia Hughes, Geoffrey C Marks, Gail M Williams and Adèle C Green
1 From the Cancer and Population Studies Group, Queensland Institute of Medical Research, Brisbane, Australia (TII, JCvdP, MCH, and ACG), and the School of Population Health, University of Queensland, Brisbane, Australia (JCvdP, GCM, and GMW)


Background: The role of diet in the development of skin cancer is inconclusive, and the effect of the combined consumption of foods has never been reported.

Objective: We prospectively investigated the association between dietary patterns and cutaneous basal cell (BCC) and squamous cell (SCC) carcinoma.

Design: Principal components analysis of 38 food groups was used to identify dietary patterns in 1360 adults aged 25–75 y who participated in a community-based skin cancer study in Nambour, Australia, between 1992 and 2002. We obtained baseline information about diet, skin color, and sun exposure factors. Multivariate-adjusted relative risks (RRs) for BCC and SCC tumors were estimated by using negative binomial regression modeling.

Results: Two major dietary patterns were identified: a meat and fat pattern and a vegetable and fruit pattern. The meat and fat pattern was positively associated with development of SCC tumors (RR = 1.83; 95% CI: 1.00, 3.37; P for trend = 0.05) after adjustment for confounders and even more strongly associated in participants with a skin cancer history (RR = 3.77; 95% CI: 1.65, 8.63; P for trend = 0.002) when the third and first tertiles were compared. A higher consumption of the vegetable and fruit dietary pattern appeared to decrease SCC tumor risk by 54% (P for trend = 0.02), but this protective effect was mostly explained by the association with green leafy vegetables. There was no association between the dietary patterns and BCC tumors.

Conclusion: A dietary pattern characterized by high meat and fat intakes increases SCC tumor risk, particularly in persons with a skin cancer history.

JAAD Melanoma Issue

The latest issue of JAAD has a series of articles that might interest bloggers including one challenging our ideas of the differences in distribution of melanomas in men and women the following link will take you to the Science Direct page for easy access to the abstracts of some of these articles.

Merkel cell Carcinoma

This is a rare condition. It is seldom diagnosed clinically. We are still working out the best way to treat it. A combined approach with wide excision and radiotherapy done immediately after the excision appears to be the best approach.

Radiotherapy for localised and advanced Merkel cell carcinoma of the skin: a single institution case series

European Journal of Dermatology. Volume 17, Number 3, 229-33, May-June 2007, Therapy


Author(s) : Falk Roeder, Robert Krempien, Florian Sterzing, Angela Funk, Martina Treiber, Jürgen Debus, Marc Bischof

Summary : Merkel cell carcinoma (MCC) is a rare malignant tumour of the skin with a tendency to rapid local progression, frequent spread to regional lymph nodes and distant metastases. We report results with radiotherapy in the treatment of MCC.Thirty-nine patients with histologically proven MCC were treated. Fifteen patients had stage I disease (12 primary, 3 recurrent tumours). Twenty-one patients had stage II disease (10 primary, 11 recurrent tumours). Thirty patients were treated with surgery and adjuvant radiotherapy. Six patients with inoperable disease received radiotherapy alone. Three patients in stage III with distant metastases were treated with palliative radiotherapy.For stage I patients, 3-year loco-regional control (LC), disease-specific survival (DSS) and overall survival (OS) rates were 90%, 100%, and 100%, respectively. For stage II patients, LC, DSS, and OS were 78%, 55%, and 29%, respectively. LC did not differ significantly between stage I and II patients. But, patients presented to radiotherapy directly after operation showed significantly improved LC compared to patients referred in recurrent situation (p \= 0.039). Two of six inoperable patients treated with radiotherapy alone relapsed locally.In the current study, surgery and immediate adjuvant radiotherapy resulted in strong loco-regional control. Radiotherapy alone is suggested only in inoperable or metastatic MCC.

SCC of the Nail

Squamous cell carcinoma of the nail apparatus: clinicopathological study of 35 cases
Authors: Dalle, S.1; Depape, L.2; Phan, A.1; Balme, B.; Ronger-Savle, S.1; Thomas, L.1

Source: British Journal of Dermatology, Volume 156, Number 5, May 2007, pp. 871-874(4)

Abstract:

Summary Background 

Subungual squamous cell carcinoma (SCC) is rare. Its diagnosis is often missed or delayed because the clinical presentation is often atypical and can mimic other conditions such as verruca vulgaris, onychomycosis, trauma-induced nail dystrophy or exostosis. Objectives 

To define the different clinical presentations and the main pathological features and to evaluate the most appropriate surgical management of subungual SCC. Methods 

A retrospective review of all the cases of subungual SCC seen in our institution over a 5-year period.
Results 
Thirty-five cases were selected. The spectrum of the clinical features encountered was extremely large including leuconychia, subungual hyperkeratosis, trachonychia, subungual tumoral syndrome, longitudinal erythronychia and melanonychia. Most cases (31 of 35) were invasive. Relapse rate after surgical treatment was low after wide surgical excision (5%) of the nail apparatus or amputation of the digit. However, limited surgical excision led to more frequent relapses (56%). Conclusions 

Nail apparatus SCC is often misdiagnosed. Most cases are invasive at the time of diagnosis. Wide surgical excision bears a lower risk of relapse. Micrographic surgery should be considered for a better control in cases treated with limited surgical excision.

Imiquimod and Atypical Nevi

This article tries to draw some conclusions about the treatment of atypical nevi with Imiquimod but there were only three cases. In essence it says do not do it and urges caution about its use in treating lentigo maligna. (IMCC)
Treatment of Atypical Nevi With Imiquimod 5% CreamNajwa Somani, MD, FRCPC; Magdalena Martinka, MD, FRCPC; Richard I. Crawford, MD, FRCPC; Jan P. Dutz, MD, FRCPC; Jason K. Rivers, MD, FRCPC


Arch Dermatol. 2007;143:379-385.

ABSTRACT

Background 5% Imiquimod cream is a topical immune response modifier that has been used off-label to treat malignant melanocytic proliferations such as lentigo maligna. To our knowledge, imiquimod has not been previously used to treat atypical nevi (AN).

Observations Three patients each with 1 selected clinically AN were treated with imiquimod 5 nights per week for 12 weeks. The lesions were subsequently excised and sent for routine histologic and immunohistochemical analysis. None of the lesions cleared. Two were consistent with atypical compound nevus on excisional biopsy and demonstrated inflammation, while the third showed congenital features and demonstrated minimal inflammation. The AN were initially interpreted as displaying more severe histologic atypia on excisional biopsy than was present at baseline. Immunohistochemical studies revealed that the AN but not the congenital-like nevus exhibited increased staining for CD4+ and CD8+ cells and for a surrogate marker of interferon expression.

Conclusions Twelve weeks of imiquimod treatment failed to cause lesional resolution. A differential inflammatory response was observed between the AN and the congenital-like nevus. The character of the inflammatory infiltrate was similar to that observed with halo nevi. Uncertainties remain concerning imiquimod use for chemoprevention of AN, and the posttreatment histologic features may be misinterpreted as severe melanocytic atypia or melanoma.

Melanoma of the Foot and Ankle

This article from Hugh Greenaway from San Diego looks at a series of melanomas on the foot and ankle. You can access the article in a Wordfile here.

Melanoma of the Foot and Ankle: A Case Series of an Underrecognized Entity
Melanoma is the most common malignancy of the foot and is more likely to be misdiagnosed on the foot than in any other location. Clinical mimics include verruca, onychomycosis, subungual hematoma, or ischemic digits.

Report of Cases

Recently at our institution, we treated 8 melanomas of the foot or ankle over a 6-month period. After obtaining institutional review board approval, we gathered the clinical data of patients with melanoma presenting to our clinic between July 1, 2003, and December 31, 2003, from our cutaneous surgery unit database at Scripps Clinic, La Jolla, Calif. Of the 69 melanomas treated in our unit during this 6-month interval, 8 melanomas (12%) were located on the foot and ankle, in contrast to our 21-year incidence of 4% (January 1985–December 2005, unpublished data). Clinical and pathologic characteristics of these 8 patients were reviewed and compared (Table).

Early markers of Mycosis Fungoides

This article explains some of the latest research confirming digitate dermatosis is a T cell lymphoma of the skin.(IMCC)

CD13 and TCR Clone: Markers of Early Mycosis Fungoides
Issue: Volume 87, Issue 2, March 2007

Pages: 155-159

DOI: 10.2340/00015555-0197

Abstract:
Making a differential diagnosis between early mycosis fungoides (MF) and parapsoriasis is often difficult at the clinical and histological level. The aim of this study was to explore markers that could help in this process. A total of 88 patients were included in 2 categories: large plaque parapsoriasis and digitiform parapsoriasis. A histological examination was performed for each patient, and expression of the antigen My7 (CD13), which is lacking in cutaneous T-lymphomas (CTCL) (but not in inflammatory lesions) and rearrangement of the T-cell receptor gene were analysed. A histological aspect of epidermo­tropic CTCL was observed in 23.5% of cases of large plaque parapsoriasis and 15% of cases of digitiform para­psoriasis. A disappearance of My7 antigen was noted in the 2 forms of parapsoriasis, more frequently when there was CTCL histology. A cutaneous clone was observed in 10.3% of cases of large plaque parapsoriasis, but not of digitiform parapsoriasis. For 3 patients, a cutaneous clone and a disappearance of My7 were associated with a non-specific histology. Considering these histological, immunological and molecular biological data, it appears that My7 antigen combined with T-cell clone may help the dermatologist to confirm the diagnosis of early MF. Moreover, further studies will determine whether CD13 is an early prognostic marker of evolution of a para­psoriasis to MF. Finally, these results demonstrate that digitiform parapsoriasis can be an early stage of MF.

Authors:
Claire Bernier, Jean Michel Nguyen, Gaëlle Quéreux, Jean Jaques Renault, Brigine Bureau and Brigitte Dreno

Poopyfield Bleeding Sign

Has anyone confidently seen this sign? (IMCC)
Poppyfield Bleeding: a New Dermatoscopic Sign and its Histopathological Background
Henrik F. Lorentzen, Kaare Weismann, Kristian Rossen and Henrik Klem Thomsen

Dermatoscopy increases the accuracy of diagnosis of melanoma. An atypical vascular pattern may be an indicator of cutaneous malignant melanoma (CMM). During dermatoscopy of certain CMMs numerous ruby droplets of blood appear when the dermatoscope is pressed firmly against the lesion. The aim of this paper was to examine the histopathological background for this observation. CMMs from 8 patients showing the poppyfield sign, i.e. squirts of ruby blood droplets, were paired with 8 CMMs of equal Breslow thickness not showing this sign. The 16 CMMs were placed in an unsystematic sequence and presented to two dermato-pathologists who assessed the lesions independently for confirmation of Breslow thickness, Clark level, ulceration and presence of dilat­ed tumour vessels. There was no disagreement between the pathologists' assessments. Age of the patients and Breslow thickness of the cutaneous malignant melanoma were similar in the two groups. All 8 poppyfield CMMs had dilated tumour vessels compared with 25% (2/8) of the non-poppyfield CMMs (p< 0.007). Histological ulceration was observed in all poppyfield CMMs and none of the non-poppyfield CMMs (p< 0.001). The poppyfield bleeding sign is a dermatoscopic clue to dilated tumour vessels. It may be a dermatoscopic reflection of increased vascular density described in primary CMMs compared with adjacent skin and may also reflect the presence of primitive vessels in CMMs displaying increased fragility.