Primary Cutaneous Malignancies Research Articles

Concurrence of Multiple Cutaneous Malignancies on Sun-exposed Vitiligo Skin of a Patient: A Case Report and Review of the Literature.

There are very few published studies in the literature examining the association between vitiligo and skin cancers and only some anecdotal reports about phototherapy-associated nonmelanoma skin carcinoma (NMSC) in patients with vitiligo. Herein, we report a case of an 84-year-old male with widespread vitiligo with concurrent onset of two primary cutaneous malignancies in sun-exposed vitiligo skin. The association between vitiligo and NMSC deserves further assessment. Chronic sun damage might be a possible causative factor for the development of NMSC in the vitiligo patient.

Primary cutaneous malignancies in the Northern Cape Province of South Africa: A retrospective histopathological review.

Excessive sun exposure and a high prevalence of HIV increase skin cancer risk in South Africa (SA). To describe the nature and extent of skin cancers presenting in the public and private health sectors of the Northern Cape Province of SA. A retrospective analysis of histologically confirmed new primary cutaneous malignancies from 1 January 2008 to 31 December 2012 was conducted using public and private health sector databases. Types, quantity and distribution of common invasive malignancies by population group, age, gender, anatomical site and health sector were explored. One-year cumulative incidence was calculated and logistic regression models were used to analyse incidence and melanoma thickness trends. A total of 4 270 biopsies (13 cutaneous malignancies) were identified. The commonest was squamous cell carcinoma (SCC), followed by basal cell carcinoma, Kaposi's sarcoma (KS), cutaneous malignant melanoma (CMM) and basosquamous carcinoma, in descending order. The odds of a white male developing SCC increased by 8% each year (odds ratio (OR) 1.08, 95% confidence interval (CI)1.01 - 1.15; p=0.022), while the odds of a black male developing SCC and KS decreased by 9% (OR 0.91, 95% CI 0.84 - 0.99; p=0.033) and 18% (OR 0.82, 95% CI 0.70 - 0.97; p=0.022), respectively, each year. SCC and CMM were diagnosed at more advanced stages in the public than in the private healthcare sector. CMM is being detected earlier, as indicated by low-stage depth increasing by 72% annually (OR 1.72, 95% CI 1.04 - 3.01; p=0.042). Results suggest that reported skin cancer patterns are changing. There is a need for further research and equitable appropriation of financial resources and effort towards developing primary skin cancer prevention initiatives in SA.

Primary cutaneous malignancies in the Northern Cape Province of South Africa: A retrospective histopathological review

NCD and AM made substantial contributions to the conception and design of the study and revised the manuscript critically. KY drafted the manuscript and acquired and interpreted the data. NPK assisted with interpretation and presentation of the data and revised the manuscript critically for intellectual content. RK implemented statistical analyses and assisted with presentation and interpretation of the results. CYW and PEK advised during the course of the study, and CYW assisted with manuscript preparation for submission.

Expression Profile of Bcl-2 in Malignant Skin Tumors

Skin is the largest organ in the body and is most commonly affected by neoplasms. In the United States only, approximately 1.2 million cases of nonmelanoma skin cancer and 80,000 cases of melanoma are diagnosed annually. A large number of families of genes that regulate apoptosis have been identified in both normal and malignant cells. There is loss of bcl-2 protein expression with increasing tumor progression. The present study was undertaken to determine the presence and possible role of bcl-2 in primary cutaneous malignancies using immunohistochemical technique and was carried in the Department of Pathology, Government Medical College, Srinagar. Fifty surgical specimens were obtained from the surgical pathology files of Department of Pathology. Imnunohistochemical study was performed. Out of the fifty cases included in the present study, only twenty one cases (42.00%) were positive for bcl-2 oncoprotein while as twenty nine cases (58%)-exhibited negativity. Basal cell carcinomas constituted 38.10% of the total positive cases, followed by Malignant Melanoma (28.57%) where as Keratoacanthomas accounted for only 4.76% positive cases. Squamous cell carcinoma and Bowen's disease constituted 14.28% each to the positive cases.

Trends in incidence of primary cutaneous malignancies in children, adolescents, and young adults: A population-based study

Skin cancer incidence among young adults is rising; however, the epidemiological characteristics of primary cutaneous lymphomas and cutaneous soft tissue sarcomas (CSTS) in individuals <30 years old has not been investigated. We analyzed the incidence and time-trends of primary cutaneous malignancies in children and adolescents/young adults (AYA). SEER-17 and -13 data were used to assess the descriptive epidemiology and time-trends in incidence of primary cutaneous malignancies in children and AYA. SEERStat and Joinpoint softwares were utilized to estimate annual percent changes (APC) in incidence. In total, 7,814 cases (ASR = 25.66/1,000,000 habitants) of primary skin cancers in <30 years old were diagnosed in 2000-2008. Females had a higher incidence of melanoma (risk ratio (RR) = 1.95; P < 0.001) and a lower risk of developing CSTS (RR = 0.64, P < 0.001). Compared to whites, blacks have a lower incidence of melanoma (RR = 0.03, P < 0.001), and higher risk of CSTS (RR = 2.28, P < 0.001). Melanoma increased in females over a 15-year period (1992-2006) (APC = 2.5, 95%CI = 1.8; 3.2), and the incidence of cutaneous T-cell lymphomas increased over the period 1992-2008 (APC = 9.5, 95% CI = 6.7; 12.4). CSTS incidence decreased among males over the period 1992-1999 (APC = -21.4, 95% CI -27.2; -15.1), particularly due to a decrease in Kaposi sarcoma incidence (AAPC 1992-2008 = -13.6, 95% CI = -22.4;-3.8), although with a notable racial disparity (whites, AAPC = -15.2, 95% CI = -23.2;-6.4; blacks, AAPC = -10.6, 95% CI = -13.2;-7.9). Non-melanoma skin cancer is very rare in children and AYA. We have shown variation in time-trends in incidence as well as in incidence patterns by race, sex, age, and histologic type, highlighting the importance of descriptive epidemiology to better understand the characteristics of these malignancies.

Simulators of Squamous Cell Carcinoma of the Skin: Diagnostic Challenges on Small Biopsies and Clinicopathological Correlation

Squamous cell carcinoma (SCC) is a common and important primary cutaneous malignancy. On skin biopsies, SCC is characterized by significant squamous cell atypia, abnormal keratinization, and invasive features. Diagnostic challenges may occasionally arise, especially in the setting of small punch biopsies or superficial shave biopsies, where only part of the lesion may be assessable by the pathologist. Benign mimics of SCC include pseudoepitheliomatous hyperplasia, eccrine squamous syringometaplasia, inverted follicular keratosis, and keratoacanthoma, while malignant mimics of SCC include basal cell carcinoma, melanoma, and metastatic carcinoma. The careful application of time-honored diagnostic criteria, close clinicopathological correlation and a selective request for a further, deeper, or wider biopsy remain the most useful strategies to clinch the correct diagnosis. This review aims to present the key differential diagnoses of SCC, to discuss common diagnostic pitfalls, and to recommend ways to deal with diagnostically challenging cases.

Skin Cancers of the Hand

Skin cancers of the hand are uncommon and poorly documented. The objective of this study was to review a large cohort of patients with hand skin malignancies to determine tumor characteristics, management techniques, and outcomes. A retrospective review of consecutive patients with surgically excised primary cutaneous hand malignancies at the John Radcliffe Hospital between 1993 and 2010 was performed. Records were reviewed to determine tumor characteristics, demographics, and management details. Outcome parameters included margins and completeness of excision, recurrence, metastatic spread, and survival. A total of 407 patients (65.8 percent male; mean age, 72.2 ± 0.7 yr) presented with 541 primary cutaneous hand malignancies and were followed up for a mean period of 24 months. Half the cohort had previous skin cancers and almost one in five developed further hand skin cancers. Squamous cell carcinoma comprised 78.0 percent, basal cell carcinoma 11.3 percent, and melanoma 3.9 percent of cases. Incidence was highest on the dorsum of the hand. Surgical margins were proportionate to tumor size, and most defects required soft-tissue reconstruction. Recurrence was uncommon in melanoma and rare in squamous and basal cell carcinomas. Lymph node metastasis and death were rare in patients with squamous cell carcinoma but relatively common in those with melanoma. Squamous cell carcinomas are the most common skin malignancy of the hand, frequently require soft-tissue reconstruction, and those occurring in the web spaces or on the dorsum of the proximal phalanges are more sinister malignancies with a greater propensity for metastatic spread. Risk, IV.

Reconstruction of Post–Radical Parotidectomy Defects

Radical parotidectomy presents a unique combination of reconstructive challenges. The high visibility of the region and the specialized structures involved create an interdependence between aesthetics and function. This article describes the authors' surgical concepts and experience in post-radical parotidectomy reconstruction. The various components of reconstruction following radical parotidectomy, including contour restoration, skin coverage, mandible reconstruction, and facial reanimation, are reviewed. The authors discuss their methods of choice and specific technical refinements. Twenty-one post-radical parotidectomy reconstruction patients (male:female, 17:4; median age, 75 years) treated from July of 2006 through May of 2010 were identified. Information on patient demographics, etiology, reconstruction technique, surgical complications, postoperative adjuvant radiotherapy, and survival was obtained. The most common indication for radical parotidectomy was metastatic cutaneous squamous cell carcinoma, followed by carcinoma ex pleomorphic adenoma and direct extension from primary cutaneous malignancy. The authors' standard approach in reconstruction was a combination of anterolateral thigh free flap and cervicofacial rotation advancement flap, repair of the facial nerve with the nerve to the vastus lateralis segmental interpositional graft, gold weight loading of the upper eyelid, lateral canthopexy, temporalis and digastric muscle transfers, and a delayed brow lift. Surgical complications include undercorrection of facial reanimation, gold weight extrusion, wound breakdown, and infections. Seventeen patients (81 percent) received adjuvant radiotherapy (range, 50 to 66 Gy to the primary site, 40 to 60 Gy to the neck). Radical parotidectomy is a morbid procedure that is sometimes necessary for oncologic control. With sound principles and attention to detail in reconstruction, however, quality of life can be greatly improved. Therapeutic, V.

Dermatoscopic vascular patterns in cutaneous Merkel cell carcinoma

Merkel cell carcinoma (MCC) is one of the most aggressive primary cutaneous malignancies. The clinical diagnosis of MCC is often delayed. Although the rarity of this skin cancer partially explains the low clinical suspicion by physicians, the absence of characteristic clinical features contributes to the delay in diagnosis. Dermatoscopy has proven a useful diagnostic tool in other cutaneous malignancies; however, the dermatoscopic features of cutaneous MCC are unknown. We performed dermatoscopy on 10 primary cutaneous MCC to describe the dermatoscopic features and correlate these findings with the histopathologic parameters. Consecutive patients with cutaneous MCC were identified and their tumors were evaluated under dermatoscopy. An 8-point MCC histopathology profile was recorded for each primary tumor in an attempt to correlate individual parameters with dermatoscopic features. All 10 tumors showed an irregular vascular pattern under dermatoscopy and demonstrated milky-red areas/globules and numerous linear irregular vessels. No correlation was noted between dermatoscopic and histopathologic features. The patients were from a single institution and tumors evaluated by a single dermatoscopic reviewer. Because of the rarity of this tumor, a small number of tumors were evaluated (10). MCC exhibits a variety of dermatoscopic vascular patterns, most commonly milky-red areas/globules, polymorphous vessels, and linear-irregular vessels. Although we found no specific dermatoscopic pattern for MCC in our series, the polymorphous vascular pattern was atypical and suggestive of a malignant process. Further studies should be done to investigate the potential correlation between dermatoscopic features and histopathologic parameters.

Modified Approach to the Cervicofacial Rotation Flap in Head and Neck Reconstruction

Objectives: Large cutaneous defects of the cheek and external ear present a reconstructive challenge. While free tissue transfer has been increasingly used for such defects, many patients with these malignancies are poor candidates for lengthy reconstructive surgery. The cervicofacial and cervicothoracic advancement flaps have been previously described as a simple method for reconstructing defects of the face and neck. However, for large facial defects, these flaps typically require wide undermining with the final closure sometimes under tension. We describe our experience utilizing a modified approach to the cervicofacial rotation flap which has little tension of the defect closure and avoids incisions or undermining of tissue inferior to the clavicle. Study Design: Retrospective chart review. Methods: Sixteen patients underwent a modified cervicofacial rotation flap for immediate reconstruction of a cheek and/or total auriculectomy defect. Results: Primary cutaneous malignancies were the most common surgical indication, followed by parotid tumors with overlying skin involvement. Five patients had total auriculectomy defects while 11 patients had defects involving cheek skin without auriculectomy. Defect diameter size varied from 5 to 12 centimeters. Two patients required skin grafting of the donor site. Four patients had minor wound dehiscences that were treated with local wound care and allowed to close by secondary intention. Conclusions: We describe a modified approach to the cervicofacial rotation flap which minimizes undermining to provide a tension-free closure of the defect. Our approach is a simple, reliable method for coverage of large cutaneous defects involving the cheek and external ear.

Zosteriform Rash: Another Manifestation of “The Internist's Tumor”

Introduction Cutaneous metastases are a well-described manifestation of renal cell carcinoma, although papillary renal cell carcinoma appears to be less commonly associated with cutaneous metastasis than clear cell histology. Zosteriform rash has a papular or vesicular appearance in a dermatomal distribution, and it has been associated with primary cutaneous malignancies as well as metastases from hematologic and solid cancers. Zosteriform rash as a manifestation of cancer has been reviewed by other researchers; however, we are aware of no reports of renal cell carcioma that caused this unusual manifestation of malignancy, and we etail the clinical course of one of our patients in this report.

Nonsurgical Treatment of Nonmelanoma Skin Cancer

The ever-increasing incidence of primary cutaneous malignancies has heralded the need for multiple treatment options. Surgical modalities remain the mainstay of treatment of nonmelanoma skin cancer. However, it is important for the dermatologic surgeon to have an understanding of all treatment options to assist the patient in making the most informed decision possible, ultimately leading to the most favorable outcome. This article explores the available nonsurgical treatment options, their indications, and their efficacy.

Primary Cutaneous Malignancies in Sub-Saharan Africa

Cutaneous malignancies are the most common malignancies in Whites; traditionally considered rare among Blacks, their occurrence in sub-Saharan Africa is yet to be fully characterized.Data on specimens submitted between 1992 and April 2008 on all histologically proven primary cutaneous malignancies were collected from the Pathology Department, including patient age, sex, anatomic site of malignancy, and histologic diagnosis. There were 1900 patients with primary cutaneous malignancies, aged between 8 months and 110 years, with a mean age of 49 years. There were 14 different types of malignancies found, with squamous cell carcinoma representing 45% of the total. A number of the rarer types have not been reported previously, from this region.Cutaneous malignancies in Africa present a number of management challenges including the following: difficulties in early diagnosis in the dark skin, late presentation, access to treatment, and the ability to pay for the appropriate treatment. The current human immunodeficiency virus/acquired immune deficiency syndrome scourge on the continent may lead a significant increase in cutaneous malignancies, posing even bigger challenges.

Preliminary clinical and pharmacologic investigation of photodynamic therapy with the silicon phthalocyanine photosensitizer pc 4 for primary or metastatic cutaneous cancers.

Photodynamic therapy (PDT) for cutaneous malignancies has been found to be an effective treatment with a range of photosensitizers. The phthalocyanine Pc 4 was developed initially for PDT of primary or metastatic cancers in the skin. A Phase I trial was initiated to evaluate the safety and pharmacokinetic profiles of systemically administered Pc 4 followed by red light (Pc 4-PDT) in cutaneous malignancies. A dose-escalation study of Pc 4 (starting dose 0.135 mg/m2) at a fixed light fluence (135 J/cm2 of 675-nm light) was initiated in patients with primary or metastatic cutaneous malignancies with the aim of establishing the maximum tolerated dose (MTD). Blood samples were taken at intervals over the first 60 h post-PDT for pharmacokinetic analysis, and patients were evaluated for toxicity and tumor response. A total of three patients (two females with breast cancer and one male with cutaneous T-cell lymphoma) were enrolled and treated over the dose range of 0.135 mg/m2 (first dose level) to 0.54 mg/m2 (third dose level). Grade 3 erythema within the photoirradiated area was induced in patient 2, and transient tumor regression in patient 3, in spite of the low photosensitizer doses. Pharmacokinetic observations fit a three-compartment exponential elimination model with an initial rapid distribution phase (∼0.2 h) and relatively long terminal elimination phase (∼28 h), Because of restrictive exclusion criteria and resultant poor accrual, the trial was closed before MTD could be reached. While the limited accrual to this initial Phase I study did not establish the MTD nor establish a complete pharmacokinetic and safety profile of intravenous Pc 4-PDT, these preliminary data support further Phase I testing of this new photosensitizer.

Primary cutaneous follicle center lymphoma in the setting of chronic lymphocytic leukemia

Primary cutaneous malignancies arising in association with chronic lymphocytic leukemia (CLL) are notable for their atypical clinical and histological presentation. We report a 69-year-old man with a 17-year history of CLL who presented for evaluation of a well-defined red to violaceous nodule with a central depressed scar on the left lower extremity. Microscopic examination of a punch biopsy revealed an infiltrate of predominantly small lymphocytes with scattered large, atypical epithelioid cells. Immunohistochemical stains revealed diffuse positive staining of the lesional cells with CD20+ and bcl-6+ and focal positive staining with bcl-2+ (negative CD10 and CD23), findings which, in conjunction with the histology, were most compatible with a diagnosis of primary cutaneous follicle center lymphoma (PCFCL). A review of the clinical charts revealed several prior biopsies with varied diagnoses. In light of the most recent biopsy findings, all previous biopsies were re-reviewed and interpreted as PCFCL arising in the setting of CLL. Features contributing to the diagnostic conundrum in this case included an atypical clinical and histological presentation, lack of pertinent clinical history and multiple presentations at different institutions.

Merkel cell carcinoma: correlation of KIT expression with survival and evaluation of KIT gene mutational status

Merkel cell carcinoma is one of the most aggressive primary cutaneous malignancies. Because some Merkel cell carcinomas express the receptor tyrosine kinase KIT, we aimed to evaluate the correlation of KIT expression with the outcome and the presence of activating mutations in the KIT gene in Merkel cell carcinoma. A total of 49 tumors from 40 patients with a diagnosis of Merkel cell carcinoma were identified, of which 30 cases from 21 patients were used in the study. KIT expression was assessed by immunohistochemistry on formalin-fixed, paraffin-embedded material. Cases were divided into low expressors (0-1+ staining intensity) and high expressors (2-3+ staining intensity). Direct sequencing of exons 9, 11, 13, 17, and 18 of the KIT gene spanning the extracellular, juxtamembrane, and tyrosine kinase domains was performed for cases with high KIT expression. Thirty tumors from 21 patients were analyzed for KIT expression. High KIT expression was seen in 67% of the patients. Five-year survival rates in tumors expressing high versus low levels of KIT were 0% versus 57.8%, respectively; however, this dramatic difference did not reach statistical significance (P = .07). A total of 4 point mutations were identified in 18 tumors analyzed. Two of these were silent mutations involving exons 17 and 18, and 2 involved intron 16-17. Two of the identified mutations may represent novel polymorphisms. Our work suggests a correlation between KIT expression and a worse prognosis in Merkel cell carcinoma patients, raising the possibility of an active role of this receptor in tumor progression and metastasis. However, we did not identify KIT activating mutations in any of the tumors analyzed.

The Uncertain Status of Cutaneous Pseudolymphoma

Cutaneous pseudolymphomas (CPLs) include a wide range of clinicopathological presentations sharing in common the presence of clinical and histopathological features mimicking those of primary cutaneous lymphomas. Although immunophenotypical studies and molecular analysis of clonality have been shown to be reliable tools, providing significant help in the differential diagnosis between primary cutaneous lymphoid malignancy and pseudolymphoma involving the skin, the identification of an etiological agent and prolonged follow-up remain the key steps to ascertain the benign, reactive nature of a skin lymphocytic infiltrate.

Histologic mimics of perineural invasion

Perineural invasion (PNI) by primary cutaneous cancers is an important adverse risk factor. Certain benign conditions may mimic microscopic PNI. Mohs surgery is being performed more frequently on smaller primary cutaneous malignancies. While PNI may be present in these cases, it is likely to be microscopic and asymptomatic, affecting as little as one cutaneous nerve branch. Review of the literature base regarding PNI as well as contribution of original findings. Four benign entities that could easily be confused with microscopic PNI are presented. At least four benign mimics of microscopic PNI exist, important in the differential diagnosis of microscopic PNI. Knowledge of these entities should help dermatopathologists to correctly distinguish them from PNI and avoid unnecessary additional treatment.

Development and application of a real time PCR assay for detection and quantification of merkel cell virus (MCV) in archived formalin fixed paraffin embedded tissue samples of merkel cell carcinoma and other cancers

Background Merkel cell carcinoma (MCC) of the skin is a highly malignant primary cutaneous neuroendocrine malignancy. Older individuals, patients undergoing immunosuppressive therapy for organ transplant, and patients with HIV infection who are immunosuppressed are at a higher risk for developing MCC. MCC may share etiologic influences with other malignancies, and increased risks for other cancers in MCC patients have been reported. Feng et al recently identified a new human polyoma virus, Merkel Cell Virus (MCV), in MCC. The discovery of MCV raises important questions. Is MCV obligatory for MCC? The absence of the viral genome in 20 percent of the 10 MCC cases in the index study suggests that some MCC may not be associated with MCV. What is the natural reservoir for this virus? Feng et al demonstrated low levels of detection in skin samples from non-disease controls. How prevalent is an MCV latent or active infection? Can detection be carried out in archived formalin fixed paraffin embedded (FFPE) tissue samples of MCC to clarify the association between MCV and MCC? Until such time as tools for serology are available polymerase chain reaction (PCR) based detection methods, particularly those that can effectively be applied to small and FFPE samples, will be valuable. Methods A real time PCR assay for MCV was developed using a known source of fresh, frozen MCC with confirmed integrated MCV kindly provided by Dr. Patrick Moore, University of Pittsburgh. The assay readily and reproducibly amplified MCV DNA. To test the assay in FFPE tissues, we assembled a 25-case series of primary and metastatic MCC archived from 1994 to 2008. A tissue microarray (TMA) was constructed to confirm the MCC diagnosis by a battery of immunohistochemistry tests. These 25 FFPE samples included MCC from 22 individual patients some with and some without known immunodeficiency. Duplicate diagnostic blocks were available from nine patients. The PCR samples were coded off site so the identity and interrelationships of the samples were unavailable to persons performing the PCR assay. In addition to reagent controls, we included DNA from 12 colon carcinomas and 20 breast carcinomas.

Elective Parotidectomy in the Management of Advanced Auricular Malignancies

The purpose of this study is to determine whether elective parotidectomy is necessary in patients with clinically and radiographically N0 parotid disease with isolated primary auricular nonmelanoma cutaneous malignancies. Auricular malignancies are typically managed by wedge resection or wide local excision. Although small lesions are easily managed by conservative excision, large bulky tumors, those with multifocal involvement, and recalcitrant lesions, often require more extensive resection including total auriculectomy, parotidectomy, and/or neck dissection. A 10-year retrospective case review from four tertiary university medical centers from 1992 to 2002. Information was retrospectively retrieved using a database of patients from the department of pathology. Seventy-one charts were reviewed. Patients with a clinical history of advanced nonmelanoma auricular carcinoma undergoing elective parotidectomy and/or neck dissection with clinically and radiographically N0 nodal disease were evaluated for the presence of occult parotid metastasis. All patients underwent parotidectomy in conjunction with a total auriculectomy for surgical extirpation of their primary auricular carcinoma. Parotid specimens were evaluated for histopathologic evidence of metastatic neoplastic disease. Pathological examination showed no histological evidence of occult parotid metastasis in all 19 patients who underwent elective parotidectomy in the presence of clinically and radiographically N0 nodal disease of the parotid or cervical regions. Parotidectomy may not be necessary in the surgical management of advanced auricularcarcinoma in the absence of clinically positive parotid disease or external auditory canal involvement.