Publications by authors named "Siegrid S Yu"

41 Publications

Recent advances in Merkel cell carcinoma.

F1000Res 2019 26;8. Epub 2019 Nov 26.

Department of Dermatology, University of California San Francisco, 1701 Divisadero Street, San Francisco, CA, 94115, USA.

Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer that has been historically associated with limited treatment options and poor prognosis. In the past 10 years, research in MCC has progressed significantly, demonstrating improved outcomes when treating with immunotherapy, particularly PD-1/PD-L1 inhibitors, when compared with conventional chemotherapy. There is also increasing evidence of the abscopal effect, a phenomenon describing the regression of untreated, distant MCC tumors following local radiation therapy. Additionally, antibodies to Merkel cell polyomavirus oncoproteins have been found to correlate with disease burden in a subset of patients, providing a useful tool for surveillance after treatment. Guidelines for the management of MCC will likely continue to change as research on surveillance and treatment of MCC continues.
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http://dx.doi.org/10.12688/f1000research.20747.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6880270PMC
January 2020

Sebaceous carcinoma: evidence-based clinical practice guidelines.

Lancet Oncol 2019 12;20(12):e699-e714

Department of Dermatology, University of Minnesota, Minneapolis, MN, USA.

Sebaceous carcinoma usually occurs in adults older than 60 years, on the eyelid, head and neck, and trunk. In this Review, we present clinical care recommendations for sebaceous carcinoma, which were developed as a result of an expert panel evaluation of the findings of a systematic review. Key conclusions were drawn and recommendations made for diagnosis, first-line treatment, radiotherapy, and post-treatment care. For diagnosis, we concluded that deep biopsy is often required; furthermore, differential diagnoses that mimic the condition can be excluded with special histological stains. For treatment, the recommended first-line therapy is surgical removal, followed by margin assessment of the peripheral and deep tissue edges; conjunctival mapping biopsies can facilitate surgical planning. Radiotherapy can be considered for cases with nerve or lymph node involvement, and as the primary treatment in patients who are ineligible for surgery. Post-treatment clinical examination should occur every 6 months for at least 3 years. No specific systemic therapies for advanced disease can be recommended, but targeted therapies and immunotherapies are being developed.
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http://dx.doi.org/10.1016/S1470-2045(19)30673-4DOI Listing
December 2019

Cranial neuropathies as the presenting symptom of cutaneous squamous cell carcinoma.

JAAD Case Rep 2019 Dec 16;5(12):1037-1040. Epub 2019 Nov 16.

The Department of Dermatology, University of California, San Francisco, California.

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http://dx.doi.org/10.1016/j.jdcr.2019.10.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6864392PMC
December 2019

A Review of the Use of Telemedicine in Dermatologic Surgery.

Dermatol Surg 2020 04;46(4):501-507

Department of Dermatology, University of California San Francisco, San Francisco, California.

Background: Telemedicine is an emerging field with numerous applications within medicine. Previous review articles describe its use within plastic surgery and otolaryngology but none, to the authors' knowledge, within dermatologic surgery.

Objective: To provide a review of the applications of telemedicine within dermatologic surgery.

Materials And Methods: A PubMed search of articles published on teledermatology was conducted in July 2018. Articles were selected based on their relevance to dermatologic surgery and reviewed for their discussion of the applications of telemedicine in surgical and cosmetic dermatology.

Results: The initial search resulted in 156 articles. Eleven ultimately met inclusion criteria: 2 in referral and consultation, 5 in telepathology, 2 in intraoperative uses, and 2 in postprocedural care.

Conclusion: For preoperative consultation, teledermatology enables the surgeon to plan ahead and increases access to care by reducing the number of clinic visits. Telepathology has the potential to allow intraoperative consultation with a dermatopathologist to achieve accurate tumor clearance without delay. Smartglasses represent a promising technology for greater care coordination and a teaching tool. Postprocedural monitoring via text messaging provides convenient access to expert advice and early detection of postoperative complications. With increasing technologic advancements, telemedicine holds great potential to augment the dermatologic surgeon's daily practice.
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http://dx.doi.org/10.1097/DSS.0000000000002230DOI Listing
April 2020

Evidence-Based Clinical Practice Guidelines for Microcystic Adnexal Carcinoma: Informed by a Systematic Review.

JAMA Dermatol 2019 Sep;155(9):1059-1068

Division of Mohs and Dermatological Surgery, Department of Dermatology and Cosmetic Dermatology, Henry Ford Hospital, Detroit, Michigan.

Importance: Microcystic adnexal carcinoma (MAC) occurs primarily in older adults of white race/ethnicity on sun-exposed skin of the head and neck. There are no formal guiding principles based on expert review of the evidence to assist clinicians in providing the highest-quality care for patients.

Objective: To develop recommendations for the care of adults with MAC.

Evidence Review: A systematic review of the literature (1990 to June 2018) was performed using MEDLINE, Embase, Web of Science, and the Cochrane Library. The keywords searched were microcystic adnexal carcinoma, sclerosing sweat gland carcinoma, sclerosing sweat duct carcinoma, syringomatous carcinoma, malignant syringoma, sweat gland carcinoma with syringomatous features, locally aggressive adnexal carcinoma, and combined adnexal tumor. A multidisciplinary expert committee critically evaluated the literature to create recommendations for clinical practice. Statistical analysis was used to estimate optimal surgical margins.

Findings: In total, 55 studies met our inclusion criteria. The mean age of 1968 patients across the studies was 61.8 years; 54.1% were women. Recommendations were generated for diagnosis, treatment, and follow-up of MAC. There are 5 key findings of the expert committee based on the available evidence: (1) A suspect skin lesion requires a deep biopsy that includes subcutis. (2) MAC confined to the skin is best treated by surgery that examines the surrounding and deep edges of the tissue removed (Mohs micrographic surgery or complete circumferential peripheral and deep margin assessment). (3) Radiotherapy can be considered as an adjuvant for MAC at high risk for recurrence, surgically unresectable tumors, or patients who cannot have surgery for medical reasons. (4) Patients should be seen by a physician familiar with MAC every 6 to 12 months for the first 5 years after treatment. Patient education on photoprotection, periodic skin self-examination, postoperative healing, and the possible normal changes in local sensation (eg, initial hyperalgesia) should be considered. (5) There is limited evidence to guide the treatment of metastasis in MAC due to its rarity. Limitations of our findings are that the medical literature on MAC comprises only retrospective reviews and descriptions of individual patients and there are no controlled studies to guide management.

Conclusions And Relevance: The presented clinical practice guidelines provide an outline for the diagnosis and management of MAC. Future efforts using multi-institutional registries may improve our understanding of the natural history of the disease in patients with lymph node or nerve involvement, the role of radiotherapy, and the treatment of metastatic MAC with drug therapy.
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http://dx.doi.org/10.1001/jamadermatol.2019.1251DOI Listing
September 2019

Atypical Fibroxanthoma.

Semin Cutan Med Surg 2019 Mar 1;38(1):E65-E66. Epub 2019 Mar 1.

Department of Dermatology, University of California San Francisco, San Francisco, CA.

Atypical fibroxanthoma (AFX) is a dermal spindle-cell sarcoma that is considered a superficial and clinically benign presentation of pleomorphic dermal sarcoma, malignant fibrous histiocytoma, and undifferentiated pleomorphic sarcoma. AFX appears clinically as a discrete red or pink nodule or papule, most commonly on the head and neck region of sun-damaged elderly patients. Histologic findings on routine hematoxylin and eosin staining reveal spindle-shaped, large, and pleomorphic tumor cells throughout the dermis. Immunohistochemistry is not specific for AFX, and the diagnosis is generally one of exclusion. AFX is best treated by complete surgical excision, with Mohs micrographic surgery considered the treatment of choice. Metastasis rarely occurs, but there is a high rate of local recurrence, especially in patients who are immunosuppressed.
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http://dx.doi.org/10.12788/j.sder.2019.008DOI Listing
March 2019

Introduction, High-Risk Skin Cancer.

Authors:
Siegrid S Yu

Semin Cutan Med Surg 2019 Mar 1;38(1):E64. Epub 2019 Mar 1.

Professor of Dermatology Director, Micrographic Surgery and Dermatologic Oncology Fellowship University of California, San Francisco, CA.

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http://dx.doi.org/10.12788/j.sder.2019.011DOI Listing
March 2019

Vulvar basal cell carcinoma in a patient with long-standing lichen sclerosus.

JAAD Case Rep 2019 Jan 9;5(1):69-71. Epub 2018 Dec 9.

Department of Dermatology, The University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.

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http://dx.doi.org/10.1016/j.jdcr.2018.07.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6290116PMC
January 2019

Transcriptional Programming of Normal and Inflamed Human Epidermis at Single-Cell Resolution.

Cell Rep 2018 10;25(4):871-883

Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA. Electronic address:

Perturbations in the transcriptional programs specifying epidermal differentiation cause diverse skin pathologies ranging from impaired barrier function to inflammatory skin disease. However, the global scope and organization of this complex cellular program remain undefined. Here we report single-cell RNA sequencing profiles of 92,889 human epidermal cells from 9 normal and 3 inflamed skin samples. Transcriptomics-derived keratinocyte subpopulations reflect classic epidermal strata but also sharply compartmentalize epithelial functions such as cell-cell communication, inflammation, and WNT pathway modulation. In keratinocytes, ∼12% of assessed transcript expression varies in coordinate patterns, revealing undescribed gene expression programs governing epidermal homeostasis. We also identify molecular fingerprints of inflammatory skin states, including S100 activation in the interfollicular epidermis of normal scalp, enrichment of a CD1CCD301A myeloid dendritic cell population in psoriatic epidermis, and IL1βCCL3CD14 monocyte-derived macrophages enriched in foreskin. This compendium of RNA profiles provides a critical step toward elucidating epidermal diseases of development, differentiation, and inflammation.
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http://dx.doi.org/10.1016/j.celrep.2018.09.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367716PMC
October 2018

In-field and abscopal response after short-course radiation therapy in patients with metastatic Merkel cell carcinoma progressing on PD-1 checkpoint blockade: a case series.

J Immunother Cancer 2018 05 30;6(1):43. Epub 2018 May 30.

Department of Radiation Oncology, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, 1600 Divisadero Street, Suite H-1031, San Francisco, CA, 94115, USA.

Background: Patients with metastatic Merkel cell carcinoma (mMCC) who experience disease progression on immunotherapy have limited additional standard options. Given evidence of synergism between radiation therapy (RT) and immunotherapy, two patients progressing on PD-1 inhibition were referred for short-course RT.

Case Presentation: Two patients were found to have progressive mMCC on PD-1 inhibitor therapy and were treated with single-fraction palliative RT. Both patients were observed to have local control at irradiated regions, as well as durable abscopal response at unirradiated, out-of-field, sites of metastatic disease.

Conclusions: Short-course RT is a compelling strategy that could be a means to augment response in patients with mMCC who show progression on immune checkpoint blockade. Ongoing clinical trials are investigating the relationship between RT and immunotherapy in mMCC.
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http://dx.doi.org/10.1186/s40425-018-0352-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5977737PMC
May 2018

Merkel cell carcinoma: An update and review: Pathogenesis, diagnosis, and staging.

J Am Acad Dermatol 2018 03 9;78(3):433-442. Epub 2017 Dec 9.

Department of Dermatology, University of California San Francisco, San Francisco, California.

Merkel cell carcinoma (MCC) is an uncommon primary cutaneous neuroendocrine cancer. It most commonly presents as an indurated plaque or nodule on sun-damaged skin in elderly patients and is characterized by high rates of local recurrence and nodal metastasis. Survival at 5 years is 51% for local disease and as low as 14% for distant disease, which underscores the aggressive nature of this tumor and challenges in management. Advances in immunology and molecular genetics have broadened our understanding of the pathophysiology of MCC and expanded our therapeutic arsenal. With this comprehensive review, we provide an update of MCC epidemiology, pathogenesis, clinical presentation, diagnostic evaluation and prognostic markers. The second article in this continuing medical education series explores the evolving landscape in MCC management.
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http://dx.doi.org/10.1016/j.jaad.2017.12.001DOI Listing
March 2018

Merkel cell carcinoma: An update and review: Current and future therapy.

J Am Acad Dermatol 2018 03 9;78(3):445-454. Epub 2017 Dec 9.

Department of Dermatology, University of California San Francisco, San Francisco, California.

Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin associated with a high risk of local recurrence and distant metastases. It most commonly occurs on sun-exposed areas of white patients >65 years of age. The Merkel cell polyomavirus (MCV) is thought to be responsible for malignant transformation in approximately 80% of cases in the northern hemisphere, while ultraviolet radiation-induced DNA damage is implicated in MCV-negative tumors. The overall incidence of MCC is low, with approximately 1600 cases diagnosed annually in the United States. The rate is much higher in patients with lymphoproliferative malignancies, solid organ transplants, and HIV infection. The low overall incidence of this tumor makes it challenging to conduct prospective clinical trials with sufficient power. As a result, most management recommendations are based on case series, retrospective reviews, and expert opinion. The pathogenesis, diagnosis, and staging of MCC was discussed in the first article in this continuing medical education series. This article focuses on current management guidelines and promising new therapies in development. Because of the complexity, aggressive nature, and individuality of each case, MCC is best treated by a multidisciplinary team.
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http://dx.doi.org/10.1016/j.jaad.2017.12.004DOI Listing
March 2018

Mental Artery Occlusion From Poly-L-Lactic Acid Injection at the Lateral Chin.

Dermatol Surg 2017 11;43(11):1402-1405

Department of Dermatology, University of California, San Francisco, San Francisco, California.

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http://dx.doi.org/10.1097/DSS.0000000000001103DOI Listing
November 2017

Merkel cell carcinoma in organ transplant recipients: Case reports and review of the literature.

JAAD Case Rep 2015 Nov 24;1(6):S29-32. Epub 2015 Nov 24.

Department of Dermatology, University of California, San Francisco, California.

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http://dx.doi.org/10.1016/j.jdcr.2015.09.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4809574PMC
November 2015

Non-tuberculous mycobacterial infections following cosmetic laser procedures: a case report and review of the literature.

J Drugs Dermatol 2015 Jan;14(1):80-3

Skin infections are not uncommon after cosmetic laser procedures. Infection rates following ablative laser resurfacing procedures are reported to be as high as 7.6%, compared to 1.9% for fractional ablation. An infrequent yet important infectious complication of ablative laser treatment is that caused by non-tuberculous mycobacteria (NTM).
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January 2015

Merkel cell carcinoma: current status of targeted and future potential for immunotherapies.

Semin Cutan Med Surg 2014 Jun;33(2):76-82

Department of Dermatology, University of California in San Francisco CA USA. Email:

Merkel cell carcinoma is an aggressive neuroendocrine tumor with a high incidence of local recurrence, regional nodal and distant metastasis, and a high mortality rate. It has been linked to a polyomavirus in addition to immune suppression. Traditionally, treatment options have been limited to surgery and radiation therapy. Better understanding of the molecular pathways of infection and carcinogenesis has provided potential molecular targets and potential immunotherapies which are discussed in this review.
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http://dx.doi.org/10.12788/j.sder.0084DOI Listing
June 2014

Organ transplant recipients with Merkel cell carcinoma have reduced progression-free, overall, and disease-specific survival independent of stage at presentation.

J Am Acad Dermatol 2014 Oct 1;71(4):684-90. Epub 2014 Jul 1.

Department of Dermatology, University of California, San Francisco, California. Electronic address:

Background: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine carcinoma of the skin. Immunosuppression is associated with increased incidence of MCC.

Objective: We sought to determine whether solid organ transplant recipients (SOTR) with MCC had decreased progression-free, disease-specific, and overall survival compared with immunocompetent patients.

Methods: We conducted a retrospective cohort study examining 8 SOTR with MCC and 89 immunocompetent control subjects. Cox regression models were generated for outcomes of progression, disease-specific death, and death from any cause, adjusted for patient sex, age at diagnosis, and stage at presentation.

Results: SOTR had a 4.1-fold increased hazard for progression (95% confidence interval 1.57-10.95, P=.004), a 10.5-fold increased hazard for all-cause mortality (95% confidence interval 3.06-35.98, P<.0001), and an 11.9-fold increased hazard for MCC-specific death (95% confidence interval 2.67-53.08, P=.001), adjusted for sex, age, and stage at presentation. SOTR had decreased 1-year overall survival, 46.8% versus 88.6%, and decreased 1-year MCC-specific survival, 56.3% versus 95.2%.

Limitations: This is a single-center study from a tertiary academic care center, and may not be generalizable to all patient populations.

Conclusions: SOTR have a significant reduction in overall, MCC-specific, and progression-free survival compared with immunocompetent patients. Further studies will determine whether aggressive treatment may improve outcomes in this high-risk population.
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http://dx.doi.org/10.1016/j.jaad.2014.05.054DOI Listing
October 2014

Relationships among primary tumor size, number of involved nodes, and survival for 8044 cases of Merkel cell carcinoma.

J Am Acad Dermatol 2014 Apr 9;70(4):637-643. Epub 2014 Feb 9.

Department of Medicine/Dermatology, University of Washington, Seattle, Washington; Fred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, Washington; Seattle Cancer Care Alliance, Seattle, Washington. Electronic address:

Background: The effects of primary tumor size on nodal involvement and of number of involved nodes on survival have not, to our knowledge, been examined in a national database of Merkel cell carcinoma (MCC).

Objective: We sought to analyze a retrospective cohort of patients with MCC from the largest US national database to assess the relationships between these clinical parameters and survival.

Methods: A total of 8044 MCC cases in the National Cancer Data Base were analyzed.

Results: There was a 14% risk of regional nodal involvement for 0.5-cm tumors that increased to 25% for 1.7-cm (median-sized) tumors and to more than 36% for tumors 6 cm or larger. The number of involved nodes was strongly predictive of survival (0 nodes, 76% 5-year relative survival; 1 node, 50%; 2 nodes, 47%; 3-5 nodes, 42%; and ≥6 nodes, 24%; P < .0001 for trend). Younger and/or male patients were more likely to undergo pathological nodal evaluation.

Limitations: The National Cancer Data Base does not capture disease-specific survival. Hence, relative survival was calculated by comparing overall survival with age- and sex-matched US population data.

Conclusion: Pathologic nodal evaluation should be considered even for patients with small primary MCC tumors. The number of involved nodes is strongly predictive of survival and may help improve prognostic accuracy and management.
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http://dx.doi.org/10.1016/j.jaad.2013.11.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3959572PMC
April 2014

Memory regulatory T cells reside in human skin.

J Clin Invest 2014 Mar 10;124(3):1027-36. Epub 2014 Feb 10.

Regulatory T cells (Tregs), which are characterized by expression of the transcription factor Foxp3, are a dynamic and heterogeneous population of cells that control immune responses and prevent autoimmunity. We recently identified a subset of Tregs in murine skin with properties typical of memory cells and defined this population as memory Tregs (mTregs). Due to the importance of these cells in regulating tissue inflammation in mice, we analyzed this cell population in humans and found that almost all Tregs in normal skin had an activated memory phenotype. Compared with mTregs in peripheral blood, cutaneous mTregs had unique cell surface marker expression and cytokine production. In normal human skin, mTregs preferentially localized to hair follicles and were more abundant in skin with high hair density. Sequence comparison of TCRs from conventional memory T helper cells and mTregs isolated from skin revealed little homology between the two cell populations, suggesting that they recognize different antigens. Under steady-state conditions, mTregs were nonmigratory and relatively unresponsive; however, in inflamed skin from psoriasis patients, mTregs expanded, were highly proliferative, and produced low levels of IL-17. Taken together, these results identify a subset of Tregs that stably resides in human skin and suggest that these cells are qualitatively defective in inflammatory skin disease.
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http://dx.doi.org/10.1172/JCI72932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3934172PMC
March 2014

18F-fluorodeoxyglucose positron emission tomography-computed tomography imaging in the management of Merkel cell carcinoma: a single-institution retrospective study.

Dermatol Surg 2013 Sep 18;39(9):1323-33. Epub 2013 Jun 18.

Department of Dermatology, University of Rochester Medical Center, Rochester, New York.

Background: Merkel cell carcinoma (MCC) is among the deadliest of cutaneous malignancies. A lack of consensus evaluation and treatment guidelines has hindered management of this disease. The utility of simultaneous positron emission tomography and computed tomography (PET/CT) has been demonstrated for a variety of tumors yet remains underinvestigated for MCC.

Objectives: To report the value of fluorodeoxyglucose PET/CT imaging in the initial staging and ongoing management of individuals with MCC and to determine whether any patient or tumor characteristics may predict when PET/CT is more likely to have greater influence on medical decision-making.

Materials And Methods: A single-institution retrospective chart review was conducted of all patients diagnosed with MCC who underwent FDG-PET/CT scanning from 2007 to 2010. The outcome of each of these studies was evaluated as to the influence on patient staging and management. Patient clinical information and information on gross and microscopic tumor characteristics were collected and analyzed.

Results: Twenty patients underwent 39 PET/CT scans. Results of PET/CT imaging revealed previously unknown information related to MCC in four (20%) patients, leading to changes in management in three of these four cases. Three previously unknown neoplasms were detected.

Conclusion: Fluorodeoxyglucose-positron emission tomography and computed tomography is a valuable tool for initial staging and to assess response to therapy of patients diagnosed with MCC. Larger prospective studies would be required to establish the optimal timing for this imaging modality.
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http://dx.doi.org/10.1111/dsu.12246DOI Listing
September 2013

Merkel cell carcinoma.

Hematol Oncol Clin North Am 2012 Dec 9;26(6):1351-74. Epub 2012 Oct 9.

Department of Dermatology, University of California, San Francisco, San Francisco, CA 94115, USA.

Merkel cell carcinoma (MCC) is a rare but aggressive carcinoma of the skin, arising most commonly in sun-exposed sites of elderly patients. The diagnosis is based on characteristic histopathologic features. In 2008, the discovery of the Merkel cell polyomavirus led to intensified research into the viral pathogenesisis of MCC. MCC staging guidelines were established in 2010, and it demonstrated the importance of distinguishing clinical vs. pathologic evaluation of lymph nodes in MCC. Surgery and/or radiation is of the mainstay of therapy for early disease, while chemotherapy is reserved for more advanced disease. Treatments based on immunologic mechanisms are currently in development.
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http://dx.doi.org/10.1016/j.hoc.2012.08.007DOI Listing
December 2012

Tobacco smoking and dermatologic surgery.

J Am Acad Dermatol 2013 Jan 25;68(1):167-72. Epub 2012 Oct 25.

Department of Dermatology, Dermatologic Surgery and Laser Center, University of California at San Francisco, San Francisco, California 94115, USA.

Background: Cigarette smoking is the leading cause of preventable death and a major public health concern. Numerous clinical and experimental studies have examined the effect of nicotine on wound healing and surgical procedures, but there are limited published reports in the dermatologic surgery literature.

Objective: This article seeks to develop evidence-based recommendations regarding the effect of tobacco use in patients undergoing dermatologic surgery procedures.

Methods: This article reviews the existing published English-language literature pertaining to the effects of tobacco on wound healing and surgical complications.

Results: Tobacco use is associated with a higher incidence of postoperative complications including wound dehiscence, flap or graft necrosis, prolonged healing time, and infections.

Limitations: This review article only summarizes past reports and studies.

Conclusion: Recommendations for smoking cessation before dermatologic surgery are provided based on the available data.
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http://dx.doi.org/10.1016/j.jaad.2012.08.039DOI Listing
January 2013

Immunohistochemical prognostication of Merkel cell carcinoma: p63 expression but not polyomavirus status correlates with outcome.

J Cutan Pathol 2012 Oct 6;39(10):911-7. Epub 2012 Aug 6.

Department of Pathology, University of Utah, Salt Lake City, UT, USA.

Merkel cell carcinoma (MCC) represents a cutaneous malignancy with high associated mortality. Numerous studies have attempted to define characteristics to more accurately predict outcome. Two recent studies have demonstrated that Merkel cell polyomavirus (MCPyV) seropositivity correlated with a better prognosis, while a third study revealed no difference. Expression of p63 by tumor cell nuclei has been shown to be associated with a worse prognosis in a European cohort. To better understand the relationship between prognosis and MCPyV or p63 status, we used immunohistochemistry to evaluate both attributes in 36 US patients with MCC. Our results show that when considered as a binary variable, p63 expression represents a strong risk factor (p < 0.0001, hazards ratio (HR) = ∞) for shortened survival. In addition, our results show that MCPyV status does not correlate with survival (p = 0.6067, HR = 1.27). Our study corroborates the European observation that p63 immunoexpression is useful as a prognostic tool. Larger studies will need to be performed in order to determine whether p63 status should be included in MCC staging, since our study is limited by its relative small size.
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http://dx.doi.org/10.1111/j.1600-0560.2012.01964.xDOI Listing
October 2012

Second-intention healing of nasal alar defects.

Dermatol Surg 2012 Apr 28;38(4):697-702. Epub 2011 Nov 28.

Department of Dermatology, University of California at San Francisco, San Francisco, California 94115, USA.

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http://dx.doi.org/10.1111/j.1524-4725.2011.02233.xDOI Listing
April 2012

Temporal dissection of tumorigenesis in primary cancers.

Cancer Discov 2011 Jul 29;1(2):137-43. Epub 2011 Jun 29.

Life Sciences Division, Lawrence Berkeley National Laboratories, USA.

Timely intervention for cancer requires knowledge of its earliest genetic aberrations. Sequencing of tumors and their metastases reveals numerous abnormalities occurring late in progression. A means to temporally order aberrations in a single cancer, rather than inferring them from serially acquired samples, would define changes preceding even clinically evident disease. We integrate DNA sequence and copy number information to reconstruct the order of abnormalities as individual tumors evolve for 2 separate cancer types. We detect vast, unreported expansion of simple mutations sharply demarcated by recombinative loss of the second copy of TP53 in cutaneous squamous cell carcinomas (cSCC) and serous ovarian adenocarcinomas, in the former surpassing 50 mutations per megabase. In cSCCs, we also report diverse secondary mutations in known and novel oncogenic pathways, illustrating how such expanded mutagenesis directly promotes malignant progression. These results reframe paradigms in which TP53 mutation is required later, to bypass senescence induced by driver oncogenes.
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http://dx.doi.org/10.1158/2159-8290.CD-11-0028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3187561PMC
July 2011

An isolated Merkel cell carcinoma metastasis at a distant cutaneous site presenting as a second 'primary' tumor.

J Cutan Pathol 2011 Oct 23;38(10):801-7. Epub 2011 Aug 23.

Department of Dermatology, University of California San Francisco, San Francisco, CA, USA.

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine carcinoma of the skin. Disease progression usually occurs via lymphatic spread to regional lymphatic draining basins, followed by distant metastasis. We report the clinical course, histopathology and genetic analysis of a 69-year-old woman with likely hematogenous spread of cutaneous neuroendocrine carcinoma manifesting as a single metastatic lesion to a distant cutaneous site. Although the possibility of two cutaneous primary MCCs was considered, array comparative genomic hybridization (aCGH) identified identical distal amplification of a region of chromosome 12p, and synchronous loss of chromosomes 8p and 17p, effectively ruling out the possibility of independent primaries. We propose that this represents a primary cheek MCC with rapid, isolated cutaneous metastasis to the contralateral ankle via hematogenous spread. The distinction between a second primary MCC and a distant cutaneous metastasis clearly has important implications with regard to staging, treatment and prognosis. To our knowledge, this represents the first report of the use of aCGH to clarify the relationship of multiple synchronous cutaneous MCCs and the first report of a single distant cutaneous focus of hematogenous spread. Our data calls into question prior reports alleging multiple cutaneous primaries of this very rare tumor.
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http://dx.doi.org/10.1111/j.1600-0560.2011.01757.xDOI Listing
October 2011

A new American Joint Committee on Cancer staging system for cutaneous squamous cell carcinoma: creation and rationale for inclusion of tumor (T) characteristics.

J Am Acad Dermatol 2011 Jun 20;64(6):1051-9. Epub 2011 Jan 20.

School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.

Background: The incidence of cutaneous squamous cell carcinoma (cSCC) is increasing. Although most patients achieve complete remission with surgical treatment, those with advanced disease have a poor prognosis. The American Joint Committee on Cancer (AJCC) is responsible for the staging criteria for all cancers. For the past 20 years, the AJCC cancer staging manual has grouped all nonmelanoma skin cancers, including cSCC, together for the purposes of staging. However, based on new evidence, the AJCC has determined that cSCC should have a separate staging system in the 7th edition AJCC staging manual.

Objective: We sought to present the rationale for and characteristics of the new AJCC staging system specific to cSCC tumor characteristics (T).

Methods: The Nonmelanoma Skin Cancer Task Force of AJCC reviewed relevant data and reached expert consensus in creating the 7th edition AJCC staging system for cSCC. Emphasis was placed on prospectively accumulated data and multivariate analyses. Concordance with head and neck cancer staging system was also achieved.

Results: A new AJCC cSCC T classification is presented. The T classification is determined by tumor diameter, invasion into cranial bone, and high-risk features, including anatomic location, tumor thickness and level, differentiation, and perineural invasion.

Limitations: The data available for analysis are still suboptimal, with limited prospective outcomes trials and few multivariate analyses.

Conclusions: The new AJCC staging system for cSCC incorporates tumor-specific (T) staging features and will encourage coordinated, consistent collection of data that will be the basis of improved prognostic systems in the future.
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http://dx.doi.org/10.1016/j.jaad.2010.08.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4659347PMC
June 2011