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1
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Shao EX, Khosrotehrani K, Campbell S, Isbel N, Green A. Pathways from Diagnosis to Death from Keratinocyte Cancer in Kidney Transplant Recipients. Dermatology 2022; 238:1036-1043. [PMID: 35439759 DOI: 10.1159/000524120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Accepted: 02/26/2022] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Kidney transplant recipients are at increased risk of developing and dying from keratinocyte cancer. We aimed to describe the clinical course of keratinocyte cancer-related deaths in a cohort of kidney transplant recipients. METHODS In kidney transplant recipients transplanted between 1995 and 2014 in Queensland, Australia, we ascertained keratinocyte cancer deaths by searching national transplant and state death registries to March 2020. Deceased transplant recipients' medical records were reviewed to assess features of the primary lesion of the fatal keratinocyte cancer, metastases, and clinical information before death. RESULTS Of 658 kidney transplant recipient deaths, 49 (7%) were due to keratinocyte cancer, and medical records were available for 36 (73%). One death was due to basal cell carcinoma, and 35 were from squamous cell carcinoma (SCC), primarily from the head and neck (24; 69%). The most common site of metastasis was the lungs (21; 58%). Median time (minimum, maximum) from the diagnosis of primary SCC to metastasis was 5 months (0, 29). After this, the median time to death was 9 months (1, 50). CONCLUSION Fatal keratinocyte cancers overwhelmingly arise on the head and neck, with lungs the most common metastasis site. The short time from diagnosis of primary to death indicates the aggressive nature of these keratinocyte cancers.
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Affiliation(s)
- Emily Ximin Shao
- QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.,The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, Queensland, Australia
| | - Kiarash Khosrotehrani
- The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, Queensland, Australia.,Department of Dermatology, Princess Alexandra Hospital Metro South, Woolloongabba, Queensland, Australia
| | - Scott Campbell
- The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, Queensland, Australia.,Department of Renal Medicine, Princess Alexandra Hospital Metro South, Woolloongabba, Queensland, Australia
| | - Nicole Isbel
- The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, Queensland, Australia.,Department of Renal Medicine, Princess Alexandra Hospital Metro South, Woolloongabba, Queensland, Australia
| | - Adele Green
- QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.,CRUK Manchester Institute and Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, United Kingdom
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2
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Mutually exclusive lymphangiogenesis or perineural infiltration in human skin squamous-cell carcinoma. Oncotarget 2021; 12:638-648. [PMID: 33868585 PMCID: PMC8021034 DOI: 10.18632/oncotarget.27915] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Accepted: 02/26/2021] [Indexed: 11/25/2022] Open
Abstract
Although tumor-associated lymphangiogenesis correlates with metastasis and poor prognosis in several cancers, it also supports T cell infiltration into the tumor and predicts favorable outcome to immunotherapy. The role of lymphatic vessels in skin squamous-cell carcinoma (sSCC), the second most common form of skin cancer, remains mostly unknown. Although anti-PD-1 therapy is beneficial for some patients with advanced sSCC, a greater understanding of disease mechanisms is still needed to develop better therapies. Using quantitative multiplex immunohistochemistry, we analyzed sSCC sections from 36 patients. CD8+ T cell infiltration showed great differences between patients, whereby these cells were mainly excluded from the tumor mass. Similar to our data in melanoma, sSCC with high density of lymphatic endothelial cells showed increased CD8+ T cell density in tumor areas. An entirely new observation is that sSCC with perineural infiltration but without metastasis was characterized by low lymphatic endothelial cell density. Since both, metastasis and perineural infiltration are known to affect tumor progression and patients’ prognosis, it is important to identify the molecular drivers, opening future options for therapeutic targeting. Our data suggest that the mechanisms underlying perineural infiltration may be linked with the biology of lymphatic vessels and thus stroma.
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3
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Tam S, Yao CMKL, Amit M, Gajera M, Luo X, Treistman R, Khanna A, Aashiq M, Nagarajan P, Bell D, El-Naggar A, Migden M, Wong M, Glisson B, Ferrarotto R, Esmaeli B, Rosenthal D, Li G, Weber RS, Myers JN, Gross ND. Association of Immunosuppression With Outcomes of Patients With Cutaneous Squamous Cell Carcinoma of the Head and Neck. JAMA Otolaryngol Head Neck Surg 2021; 146:128-135. [PMID: 31804658 DOI: 10.1001/jamaoto.2019.3751] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Importance Patients with immunosuppression have a higher incidence of cutaneous squamous cell carcinoma (cSCC) and often present with more aggressive, multifocal disease. Objectives To determine the risks for mortality in patients with cSCC and immunosuppression compared with nonimmunosuppression and to compare the difference in mortality risk based on the cause of immunocompromise. Design, Setting, and Participants This retrospective cohort study of patients with cSCC of the head and neck recruited participants from a tertiary cancer care center. Patients who underwent no treatment, wide local excision, or biopsy of the lesions were eligible for inclusion from January 1, 1995, to September 30, 2015. Data were analyzed from March 21, 2018, to April 4, 2019. Exposures Immunocompromise, defined as having solid organ transplant, stem cell transplant, hematopoetic malignant disease, autoimmune disease requiring treatment with immunosuppressive therapy, type 1 or 2 diabetes treated with insulin, HIV or AIDS, or other hematoproliferative disorder. Main Outcomes and Measures Patients were divided into 2 groups according to their immune status (immunosuppression vs no immunosuppression). The primary outcome measure was disease-specific survival. A Cox proportional hazards regression model was used to determine the association of immune status with disease outcome. Results A total of 796 patients (680 men [85.4%]; median age, 69 [range, 27-98] years), including 147 with and 649 without immunosuppression (IS and non-IS groups, respectively), constituted the final cohort. In the IS group, 77 (52.4%) had diabetes, 39 (26.5%) had lymphoma or leukemia, 25 (17.0%) had an organ or stem cell transplant, and 3 (2.0%) had HIV. Five-year disease-specific survival was 68.2% in the IS group compared with 84.1% in the non-IS group (difference, 15.9%; 95% CI, 3.5%-27.4%). Immunosuppression was independently associated with worse disease-specific survival (hazard ratio, 2.32; 95% CI, 1.53-3.50). Conclusions and Relevance This study's findings suggest that immunosuppression is independently associated with a worse outcome in cSCC, with a 2.32 times increased risk of disease-specific death after adjusting for age, history of skin cancer, recurrent or persistent disease status, disease stage, and treatment.
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Affiliation(s)
- Samantha Tam
- Division of Surgery, Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston
| | - Christopher M K L Yao
- Division of Surgery, Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston
| | - Moran Amit
- Division of Surgery, Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston
| | - Mona Gajera
- Division of Surgery, Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston
| | - Xiaoning Luo
- Division of Surgery, Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston
| | - Rachel Treistman
- Division of Surgery, Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston
| | - Anshu Khanna
- Division of Surgery, Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston
| | - Mohamed Aashiq
- Division of Surgery, Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston
| | - Priyadharsini Nagarajan
- Division of Pathology and Laboratory Medicine, Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston
| | - Diana Bell
- Division of Pathology and Laboratory Medicine, Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston
| | - Adel El-Naggar
- Division of Pathology and Laboratory Medicine, Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston
| | - Michael Migden
- Division of Internal Medicine, Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston
| | - Michael Wong
- Division of Cancer Medicine, Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston
| | - Bonnie Glisson
- Division of Cancer Medicine, Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston
| | - Renata Ferrarotto
- Division of Cancer Medicine, Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston
| | - Bita Esmaeli
- Division of Surgery, Department of Plastic Surgery, Ophthalmic Plastic Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - David Rosenthal
- Division of Radiation Oncology, Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston
| | - Guojun Li
- Division of Surgery, Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston
| | - Randal S Weber
- Division of Surgery, Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston
| | - Jeffrey N Myers
- Division of Surgery, Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston
| | - Neil D Gross
- Division of Surgery, Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston
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4
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Cheng JY, Li FY, Ko CJ, Colegio OR. Cutaneous Squamous Cell Carcinomas in Solid Organ Transplant Recipients Compared With Immunocompetent Patients. JAMA Dermatol 2019; 154:60-66. [PMID: 29167858 DOI: 10.1001/jamadermatol.2017.4506] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Importance Solid organ transplant recipients (SOTRs) have a 100-fold increased risk of squamous cell carcinoma (SCC), and they may develop more aggressive SCCs compared with immunocompetent individuals. Objective To compare outcomes associated with aggressive behavior of SCC in SOTRs and high-risk immunocompetent patients. Design, Setting, and Participants A retrospective cohort study of 58 SOTRs and 40 immunocompetent patients evaluated at the Yale Transplant Dermatology Clinic in New Haven, Connecticut, who had at least 1 SCC confirmed histopathologically between January 1, 2008, and December 31, 2015. Cumulative follow-up time for this study was 369 patient-years. Exposure Immunosuppressive medication regimen for SOTRs. Main Outcomes and Measures The primary outcome measure was tumor depth of SCC. Secondary outcome measures that reflected tumor aggressiveness included perineural invasion, regional metastases, nodal metastases, disease-specific death, and overall death. Results Of the 58 SOTR study participants, 14 were women and 44 were men; the mean (SD) age was 61.3 (8.4) years. Of the 40 immunocompetent study participants, 16 were women and 24 were men; the mean (SD) age was 69.8 (10.9) years, resulting in a statistically significant difference from the SOTR group. The mean (SD) number of years that SOTRs were immunosuppressed was 14.6 (9.2) years (range, 2-37 years). The SOTR and immunocompetent groups were statistically comparable regarding race and sex, patient care, follow-up time, numbers of skin lesions, and field cancerization and chemopreventive therapies. The SOTR group had a significantly higher annual frequency of visits (mean [SD], 4 [2] vs 3 [2] office visits per patient per year, P = .02) and annual biopsy rates (mean [SD], 6 [4] vs 5 [3] biopsies per patient per year, P = .04). The SOTRs developed SCCs that did not appear to be significantly more aggressive than those found in the immunocompetent control group. These SOTRs also did not develop significantly thicker tumors than the immunocompetent control group (median [IQR] tumor depth, 1.30 [0.90-1.60] mm in 35 SOTRs vs 1.22 [1.10-1.60] mm in 20 immunocompetent patients). Conclusions and Relevance The increased risk and the potential for aggressive behavior of SCCs in SOTRs may be successfully managed at a level comparable to that in high-risk immunocompetent individuals through close adherence to current dermatologic surveillance recommendations and a marginally lower threshold for biopsy of suspicious lesions for SOTRs.
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Affiliation(s)
- Joyce Y Cheng
- Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut
| | - Fang-Yong Li
- Yale Center for Analytical Sciences, New Haven, Connecticut
| | - Christine J Ko
- Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut.,Department of Pathology, Yale University School of Medicine, New Haven, Connecticut
| | - Oscar R Colegio
- Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut.,Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.,Department of Surgery, Yale University School of Medicine, New Haven, Connecticut.,Yale Cancer Center, Yale-New Haven Hospital, New Haven, Connecticut.,Yale Transplant Dermatology Clinic, Yale-New Haven Transplantation Center, New Haven, Connecticut
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5
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Genders RE, Weijns ME, Dekkers OM, Plasmeijer EI. Metastasis of cutaneous squamous cell carcinoma in organ transplant recipients and the immunocompetent population: is there a difference? a systematic review and meta-analysis. J Eur Acad Dermatol Venereol 2019; 33:828-841. [PMID: 30793804 DOI: 10.1111/jdv.15396] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2018] [Accepted: 11/14/2018] [Indexed: 12/24/2022]
Abstract
BACKGROUND Organ transplant recipients (OTR) have a higher risk of developing cutaneous squamous cell carcinoma (cSCC) compared to the immunocompetent population. Immunosuppression is often stated as a risk factor for metastasis. However, evidence for this is scarce. OBJECTIVES To investigate the cSCC metastasis risk in OTR and the immunocompetent population by systematically reviewing the literature. METHODS A systematic review of the literature was performed up to January 2018 using: Medline; Embase; Web of Science and ISI Science Citation Index. Studies assessing cSCC metastasis risk in ORT or immunocompetent cohorts were considered. A pooled risk estimate for metastasis was calculated for the immunocompetent population and OTR separately. RESULTS The pooled metastasis risk estimate for OTR was, respectively, 7.3% (95% CI 6.2-8.4) for cSCC on total body, and 11.0% (95% CI 7.7-14.8) for cSCC of the head neck area. For the immunocompetent population reported risk estimate analysis showed a pooled metastatic risk of 3.1% (95% CI 2.8-3.4) in total body cSCC and of 8.5% (95% CI 7.3-9.8) in cSCC of the head and neck area. Pooled risk estimate per single cSCC in OTR was 1.3% (95% CI 1.0-1.7) in total body cSCC and 4.0% (95% CI 2.7-5.5) in cSCC of the head and neck area. In the immunocompetent population, these pooled risk estimates were, respectively, 2.4% (95% CI 2.1-2.6) and 6.7% (95% CI 5.7-7.8). CONCLUSIONS Organ transplant recipients show a higher overall risk of cSCC metastasis compared to the immunocompetent population. Metastasis risks per single cSCC were substantially lower in both groups. However, due to heterogeneity and differences between studies, comparisons are difficult. Comprehensive follow-up studies with defined cohorts are necessary to adequately asses the risk for cSCC metastasis.
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Affiliation(s)
- R E Genders
- Department of dermatology, Leiden University Medical Centre, Leiden, the Netherlands.,Department of Dermatology, Roosevelt Clinics, Leiden, the Netherlands
| | - M E Weijns
- Department of dermatology, Leiden University Medical Centre, Leiden, the Netherlands
| | - O M Dekkers
- Department of clinical epidemiology, Leiden University Medical Centre, Leiden, the Netherlands
| | - E I Plasmeijer
- Department of dermatology, Leiden University Medical Centre, Leiden, the Netherlands
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Abstract
OPINION STATEMENT Non-melanoma skin cancer (NMSC) is the most common malignancy in the USA, with cutaneous squamous cell carcinomas (cSCCs) constituting approximately 20 % of all NMSC. While cSCCs typically behave in an indolent fashion and can be cured with local destructive or surgical methods, a small subset metastasizes and induces significant morbidity and mortality. Identifying and aggressively treating these "high-risk" cSCCs (HRcSCCs) is thus paramount. Recent improvements in staging cSCCs appear to offer better risk stratification than earlier staging criteria. Radiologic imaging and sentinel lymph node biopsy may be beneficial in certain cases of HRcSCC, although more studies are needed before these techniques should be uniformly incorporated into management. Surgery with complete margin control, such as that offered by the Mohs micrographic technique, represents the first-line treatment for these tumors. Radiation therapy is likely most beneficial in the adjuvant setting. Chemotherapy is typically best reserved for patients with metastatic or locally advance disease that is not controllable with surgical and/or radiation therapies. Newer targeted treatments, such as EGFR inhibitors and immunotherapies may offer greater efficacy in these settings, although further evaluation is needed.
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7
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Pyne JH, Myint E, Barr EM, Clark SP, David M, Na R. Acantholytic invasive squamous cell carcinoma: tumor diameter, invasion depth, grade of differentiation, surgical margins, perineural invasion, recurrence and death rate. J Cutan Pathol 2017; 44:320-327. [DOI: 10.1111/cup.12869] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2016] [Revised: 11/20/2016] [Accepted: 12/13/2016] [Indexed: 02/04/2023]
Affiliation(s)
- J. H. Pyne
- School of MedicineUniversity of Queensland Brisbane Australia
| | - E. Myint
- School of MedicineUniversity of Queensland Brisbane Australia
| | - E. M. Barr
- School of MedicineUniversity of Queensland Brisbane Australia
| | - S. P. Clark
- School of MedicineUniversity of Queensland Brisbane Australia
| | - M. David
- School of MedicineUniversity of Queensland Brisbane Australia
| | - R. Na
- Prince of Wales Clinical SchoolUniversity of New South Wales Sydney Australia
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8
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Abstract
The incidence of nonmelanoma skin cancer (NMSC) continues to rise, partly because of aging, the frequency of early childhood sunburns, and sporadic extreme recreational sun exposure. A nonsurgical approach to selected cutaneous malignancy could possibly reduce the cost as well as morbidity of surgical treatment for NMSC. There has been growing interest in isolating compounds that could suppress or reverse the biochemical changes necessary for cutaneous malignancies to progress by pharmacologic intervention. By targeting diverse pathways recognized as important in the pathogenesis of nonmelanoma skin cancers, a combination approach with multiple agents or addition of chemopreventative agents to topical sunscreens may offer the potential for novel and synergistic therapies in treating nonmelanoma skin cancer. This preliminary information will expand to include more therapeutic options for NMSC in the future.
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Affiliation(s)
- Prasan R Bhandari
- Department of Pharmacology, Shri Dharmasthala Manjunatheshwara College of Medical Sciences and Hospital, Sattur, Dharwad, Karnataka, India
| | - Varadraj V Pai
- Department of Dermatology, Shri Dharmasthala Manjunatheshwara College of Medical Sciences and Hospital, Sattur, Dharwad, Karnataka, India
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9
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Parikh SA, Patel VA, Ratner D. Advances in the management of cutaneous squamous cell carcinoma. F1000PRIME REPORTS 2014; 6:70. [PMID: 25165569 PMCID: PMC4126542 DOI: 10.12703/p6-70] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Cutaneous squamous cell carcinoma is one of the most common non-melanoma skin cancers worldwide. While most cutaneous squamous cell carcinomas are easily managed, there is a high-risk subset of tumors that can cause severe morbidity and mortality. Tumor characteristics as well as patient characteristics contribute to the classification of cutaneous squamous cell carcinomas as low-risk vs. high-risk. Advances in the treatment of cutaneous squamous cell carcinomas largely relate to the management of this high-risk subset. Surgical and non-surgical management options, including newer targeted molecular therapies, will be discussed here. Larger, multicenter studies are needed to determine the exact significance of individual risk factors with respect to aggressive clinical behavior and the risks of metastasis and death, as well as the role of surgical and adjuvant therapies in patients with high-risk cutaneous squamous cell carcinomas.
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Affiliation(s)
- Sonal A. Parikh
- Columbia University Department of Dermatology161 Fort Washington Ave. 12th FloorNew York, NY 10032, USA
| | - Vishal A. Patel
- Columbia University Department of Dermatology161 Fort Washington Ave. 12th FloorNew York, NY 10032, USA
| | - Desiree Ratner
- Mount Sinai Beth Israel Cancer Center West325 W. 15th streetNew York, NY 10011, USA
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10
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O’Bryan K, Sherman W, Niedt GW, Taback B, Manolidis S, Wang A, Ratner D. An evolving paradigm for the workup and management of high-risk cutaneous squamous cell carcinoma. J Am Acad Dermatol 2013; 69:595-602.e1. [DOI: 10.1016/j.jaad.2013.05.011] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2012] [Revised: 04/26/2013] [Accepted: 05/16/2013] [Indexed: 10/26/2022]
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11
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Kempf W, Mertz KD, Hofbauer GFL, Tinguely M. Skin cancer in organ transplant recipients. Pathobiology 2013; 80:302-9. [PMID: 24013135 DOI: 10.1159/000350757] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
Organ transplant recipients (OTR) are at a significantly increased risk for developing a wide variety of skin cancers, particularly epithelial skin cancer, Merkel cell carcinoma and Kaposi's sarcoma. Melanoma, skin adnexal neoplasm and cutaneous lymphomas are also more common in OTR and may differ in their clinicopathologic presentation from tumors in immunocompetent patients. The accuracy of clinical diagnosis of suspected premalignant and malignant skin lesions in OTR is modest. Therefore, histopathological diagnosis is an essential element for the diagnostic workup of skin cancers and, in addition, provides important information on prognosis. Squamous cell carcinoma and intraepithelial neoplasias (actinic keratosis, squamous cell carcinoma in situ or Bowen's disease) are the most common forms of skin cancer in OTR. The risk of Merkel cell carcinoma and Kaposi's sarcoma is dramatically increased in OTR. Merkel cell carcinoma shows a highly aggressive course. Kaposi's sarcoma tends to spread to extracutaneous sites. Primary cutaneous lymphomas developing after organ transplantation are rare. The spectrum of cutaneous B cell lymphomas in OTR, in particular, differs significantly from that of the general population, with a predominance of Epstein-Barr virus-driven posttransplant lymphoproliferative disorder. This review discusses the clinical and histopathological aspects of skin cancers in OTR, the impact of dermatopathological analysis on prognosis and the understanding of the pathogenesis of these neoplasms.
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Affiliation(s)
- Werner Kempf
- Kempf and Pfaltz Histological Diagnostics, Zurich, Switzerland
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12
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Hanlon A. Metastatic Squamous Cell Carcinoma: Epidemiology and Available Systemic Therapies. CURRENT DERMATOLOGY REPORTS 2013. [DOI: 10.1007/s13671-013-0047-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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13
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Madeleine MM, Johnson LG, Daling JR, Schwartz SM, Carter JJ, Berg D, Nelson K, Davis CL, Galloway DA. Cohort profile: the skin cancer after organ transplant study. Int J Epidemiol 2012; 42:1669-77. [PMID: 23171871 DOI: 10.1093/ije/dys179] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
The Skin Cancer after Organ Transplant (SCOT) study was designed to investigate the link between genus beta human papillomavirus (HPV) and squamous cell skin cancer (SCSC). We focused on a population receiving immunosuppressive therapy for extended periods, transplant patients, as they are at extremely high risk for developing SCSC. Two complementary projects were conducted in the Seattle area: (i) a retrospective cohort with interview data from 2004 recipients of renal or cardiac transplants between 1995 and 2010 and (ii) a prospective cohort with interview data from 328 people on the transplant waiting lists between 2009 and 2011. Within the retrospective cohort, we developed a nested case-control study (172 cases and 337 control subjects) to assess risk of SCSC associated with markers of HPV in SCSC tumour tissue and eyebrow hair bulb DNA (HPV genotypes) and blood (HPV antibodies). In the prospective cohort, 135 participants had a 1-year post-transplant visit and 71 completed a 2-year post-transplant visit. In both arms of the cohort, we collected samples to assess markers of HPV infection such as acquisition of new types, proportion positive for each type, persistence of types at consecutive visits and number of HPV types detected. In the prospective cohort, we will also examine these HPV markers in relation to levels of cell-mediated immunity. The goal of the SCOT study is to use the data we collected to gain a more complete understanding of the role of immune suppression in HPV kinetics and of genus beta HPV types in SCSC. For more information, please contact the principal investigator through the study website: http://www.fhcrc.org/science/phs/cerc/The_SCOT_Study.html.
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Affiliation(s)
- Margaret M Madeleine
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA, Department of Epidemiology, University of Washington, Seattle, WA, USA, Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA, Division of Dermatology, University of Washington, Seattle, WA, USA, Laboratory of Immunogenetics, Puget Sound Blood Center, Seattle, WA, USA, Division of Nephrology, University of Washington, Seattle, WA, USA and Department of Microbiology, University of Washington, Seattle, WA, USA
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14
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Abstract
Nonmelanoma skin cancer (NMSC) represents the most common form of cancer in Caucasians, with continuing increase in incidence worldwide. Basal cell carcinoma (BCC) accounts for 75% of cases of NMSC, and squamous cell carcinoma (SCC) accounts for the remaining majority of NMSC cases. Whilst metastasis from BCC is extremely rare, metastasis from high-risk SCC may be fatal. In this article, we review the aetiology, diagnosis and management of NMSC.
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Affiliation(s)
- Venura Samarasinghe
- Dermatology Centre, Salford Royal Hospital, NHS Foundation Trust, Stott Lane, Salford M6 8HD, UK
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15
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Abstract
Cutaneous squamous cell carcinoma (CSCC) is the second most common malignancy occurring in white patients in the United States and incidence rates are increasing. While the majority of the 87,000-760,000 cases that occur yearly in the U.S. are curable, 4% develop lymph node metastases and 1.5% die from the disease. Given the frequency of occurrence of CSCC, it is estimated to cause as many deaths yearly as melanoma, with the majority occurring in patients with high risk tumors or in those at high risk for metastasis due to a variety of host factors, most commonly systemic immunosuppression. There are currently no standardized prognostic or treatment models to assist clinicians in most effectively identifying and managing these patients. Identification of patients at risk for poor outcomes as well as standardization regarding classification, staging, and treatment of high-risk tumors is critical for optimizing patient care. In this article, available literature on the classification and management of high risk CSCC is briefly summarized, emphasizing new information.
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Affiliation(s)
- Nicole R LeBoeuf
- Department of Dermatology, Dana Farber Cancer Institute/Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02130, USA
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16
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Abstract
Cutaneous squamous cell carcinoma (SCC) is the second most common human cancer and can behave aggressively. Mohs micrographic surgery offers the highest cure rates for high-risk SCCs and is particularly useful for SCCs on challenging anatomic sites.
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Affiliation(s)
- Daniel Belkin
- Department of Dermatology, Weill Cornell Medical College, 1305 York Avenue, New York, NY 10021, USA
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17
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Allgayer H, Hart IR. Editorial: Special Section on “Site-Specific Metastasis”. Int J Cancer 2011; 128:2509-10. [DOI: 10.1002/ijc.26050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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18
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Efird JT, Toland AE, Lea CS, Phillips CJ. The combined influence of oral contraceptives and human papillomavirus virus on cutaneous squamous cell carcinoma. Clin Med Insights Oncol 2011; 5:55-75. [PMID: 21499554 PMCID: PMC3076039 DOI: 10.4137/cmo.s6905] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
The vast majority of cutaneous squamous cell carcinoma (CSCC) will occur in those with fair complexion, tendency to burn, and high ultraviolet radiation (UVR) exposure. Organ transplant recipients also are an important population at great risk for CSCC. An association has been reported between oral contraceptive (OC) use, human papillomavirus virus (HPV) and cervical cancer, and there could be a similar association for CSCC. The cutaneous HPV β-E6 protein, a close cousin of the transformative E6 protein underlying anogenital cancers, has been shown to inhibit apoptosis in response to UVR damage and stimulate morphologic transformation in rodent fibroblast cell lines. Furthermore, OC use has been shown to enhance HPV transcription and may contribute to CSCC risk through this pathway.
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Affiliation(s)
- Jimmy T. Efird
- Center for Health Disparities Research, Brody School of Medicine, East Carolina University, 1800 W. 5th Street (Medical Pavilon), Greenville, NC 27834 USA
- Department of Public Health, 1709 W. 6th Street, Mail Stop 660, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA
| | - Amanda E. Toland
- Department of Molecular Virology, Immunology and Medical Genetics, 998 Biomedical Research Tower, 460 W. 12th Avenue, The Ohio State University, Columbus, OH 43210, USA
| | - C. Suzanne Lea
- Department of Public Health, 1709 W. 6th Street, Mail Stop 660, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA
| | - Christopher J. Phillips
- Department of Defence Center for Deployment Health Research, Naval Health Research Center, Dept. 164, 140 Sylvester Rd., San Diego, CA 92106, USA
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Cutaneous squamous cell carcinoma of the head and neck. J Skin Cancer 2011; 2011:502723. [PMID: 21461387 PMCID: PMC3064996 DOI: 10.1155/2011/502723] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2010] [Revised: 10/15/2010] [Accepted: 12/15/2010] [Indexed: 12/13/2022] Open
Abstract
Cutaneous squamous cell carcinoma of the head and neck is an epidemic that reaches all parts of the world. Making the diagnosis relies on the acumen of the clinician and pathologist. Various pathologic subtypes exist and differ in histology and prognosis. High-risk tumors need aggressive treatment and vigilant surveillance to monitor for recurrence. Large tumors, deep tissue invasion, perineural involvement, recurrence, location in high-risk areas, and immunosuppression are implicated in worsening prognosis. Surgery is the mainstay of treatment with adjuvant radiation therapy as needed for aggressive tumors; however, other modalities are potentially useful for low-risk lesions. The use of Mohs surgery has become increasingly useful and has shown high success rates. Involvement of parotid and neck lymph nodes significantly affects outcomes and the physician should be comfortable with management of this complex disease. This paper examines the diagnosis, pathology, clinical course, and treatment options for cutaneous squamous cell carcinoma of the head and neck.
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21
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Surgical intervention for skin cancer in organ transplant recipients. Cancer Treat Res 2009. [PMID: 19415222 DOI: 10.1007/978-0-387-78574-5_35] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register]
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22
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McGuire JF, Ge NN, Dyson S. Nonmelanoma skin cancer of the head and neck I: histopathology and clinical behavior. Am J Otolaryngol 2009; 30:121-33. [PMID: 19239954 DOI: 10.1016/j.amjoto.2008.03.002] [Citation(s) in RCA: 62] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2008] [Accepted: 03/08/2008] [Indexed: 01/03/2023]
Abstract
Non-Melanoma skin cancer (NMSC) is the most commonly encountered malignancy in almost every area of practice, but the cases that present to an Otolaryngology practice will be advanced in nature. The major subtypes of NMSC include basal cell carcinoma, squamous cell carcinoma, dermatofibrosarcoma protuberans, merkel cell carcinoma, and adnexal malignancies. In this review, we present the epidemiology, histology, clinical presentation and management of these major subtypes. Further, we present background on multimodality treatment for NMSC lesions that have become metastatic from their primary site and an introduction to the behavior and treatment of NMSC lesions in patients who have received organ transplants. Understanding the clinical behavior of advanced NMSC is essential knowledge for a general Otolaryngologist.
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Affiliation(s)
- John F McGuire
- Department of Otolaryngology, Head and Neck Surgery, University of California, Irvine, CA 92618, USA
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23
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Drake AL, Walling HW. Variations in presentation of squamous cell carcinoma in situ (Bowen's disease) in immunocompromised patients. J Am Acad Dermatol 2008; 59:68-71. [DOI: 10.1016/j.jaad.2008.03.028] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2007] [Revised: 03/02/2008] [Accepted: 03/18/2008] [Indexed: 10/22/2022]
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Duncan FJ, Wulff BC, Tober KL, Ferketich AK, Martin J, Thomas-Ahner JM, Allen SD, Kusewitt DF, Oberyszyn TM, Vanbuskirk AM. Clinically relevant immunosuppressants influence UVB-induced tumor size through effects on inflammation and angiogenesis. Am J Transplant 2007; 7:2693-703. [PMID: 17941958 DOI: 10.1111/j.1600-6143.2007.02004.x] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Immunosuppressive therapies allow long-term patient and transplant survival, but are associated with increased development of UV-induced skin cancers, particularly squamous cell carcinomas. The mechanisms by which CsA, MMF, tacrolimus (TAC) or sirolimus (SRL), alone or in dual combinations, influence tumor development and progression are not completely understood. In the current study, chronically UV-exposed mice treated with SRL alone or in combination with CsA or TAC developed more tumors than mice treated with vehicle or other immunosuppressants, but the tumors were significantly smaller and less advanced. Mice treated with CsA or TAC developed significantly larger tumors than vehicle-treated mice, and a larger percentage in the CsA group were malignant. The addition of MMF to CsA, but not to TAC, significantly reduced tumor size. Immunosuppressant effects on UVB-induced inflammation and tumor angiogenesis may explain these findings. CsA enhanced both UVB-induced inflammation and tumor blood vessel density, while MMF reduced inflammation. Addition of MMF to CsA reduced tumor size and vascularity. SRL did not affect inflammation, but significantly reduced tumor vascularity. Thus the choice of immunosuppressants has important implications for tumor number, size and progression, likely due to the influence of immunosuppressants on UVB-induced inflammation and angiogenesis.
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Affiliation(s)
- F J Duncan
- Department of Surgery, The Ohio State University, Columbus, OH, USA
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Herman S, Rogers HD, Ratner D. Immunosuppression and squamous cell carcinoma: a focus on solid organ transplant recipients. Skinmed 2007; 6:234-8. [PMID: 17786101 DOI: 10.1111/j.1540-9740.2007.06174.x] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/17/2023]
Abstract
As transplant medicine advances, new immunosuppressive regimens are increasing the long-term survival of solid organ transplant recipients (SOTRs). This growing population is at significantly increased risk for developing cutaneous malignancies, particularly squamous cell carcinoma (SCC), as a result of chronic immunosuppression. Conventional risk factors for the development of skin cancer, including fair skin type, advanced age, sun exposure, and genetic predisposition, also play a crucial role in the initiation and progression of SCC in SOTRs. Immunosuppressed patients develop more aggressive and more numerous SCCs than immunocompetent individuals, however. It is important to understand the mechanisms underlying immunosuppression-mediated SCC development to identify prognostic markers and to develop effective prevention and treatment strategies. This article addresses the fundamental differences between SCC in SOTRs and those in the general population, focusing on the role that immunosuppression plays in the pathogenesis of this malignancy.
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Affiliation(s)
- Sara Herman
- Department of Dermatology, Columbia University Medical Center, 161 Fort Washington Avenue, New York, NY 10012, USA
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Veness MJ, Harris D. Role of radiotherapy in the management of organ transplant recipients diagnosed with non-melanoma skin cancers. ACTA ACUST UNITED AC 2007; 51:12-20. [PMID: 17217484 DOI: 10.1111/j.1440-1673.2006.01649.x] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Organ transplantation has had a major effect on the lives of thousands of patients worldwide. In Australia and New Zealand, over 13 000 patients have become organ transplant recipients (OTR). Following transplantation, patients require lifelong immunosuppression to prevent organ rejection. The loss of immune surveillance results in OTR experiencing a higher incidence of infection and malignancy in comparison with the general (immunocompetent) population. Non-melanoma skin cancer (NMSC) is the most common malignancy worldwide, arising most often on the sun-exposed head and neck. Organ transplant recipients experience a higher incidence of NMSC when compared with the general population and a higher incidence of squamous cell carcinoma compared with basal cell carcinoma. Organ transplant recipients also develop NMSC at a younger age and experience multiple new NMSC. Australians experience the highest incidence of NMSC in the world with a consequence that NMSC arising in OTR can lead to significant morbidity and even mortality. Radiation oncologists treating patients with skin cancer will almost certainly make recommendations in the setting of NMSC arising in OTR. The aim of this article is to discuss the role of radiotherapy in the management of OTR diagnosed with NMSC. The emphasis will be on the treatment of patients with a high-risk NMSC (e.g. squamous cell carcinoma, Merkel cell carcinoma, unfavourable basal cell carcinoma) because this reflects the most common clinical scenario in which a recommendation of radiotherapy, usually adjuvant, may be considered.
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Affiliation(s)
- M J Veness
- Department of Radiation Oncology, Westmead Hospital, Westmead, NSW, Australia.
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O'Reilly F, Traywick C, Pennie ML, Foster JK, Chen SC. Baseline Quality of Life and Anxiety in Solid Organ Transplant Recipients: A Pilot Study. Dermatol Surg 2006; 32:1480-5. [PMID: 17199656 DOI: 10.1111/j.1524-4725.2006.32356.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
BACKGROUND Solid organ transplant recipients on high doses of immunosuppression are at increased risk for the development of nonmelanoma skin cancer (NMSC). OBJECTIVE The objective was to assess the possible factors impacting quality of life (QOL) in solid organ transplant recipients. METHODS Patients were seen in a dermatology clinic integrated within the transplant center at a university-based hospital. One anxiety questionnaire and three QOL questionnaires were administered to each patient. A regression model was used to determine possible predictors of anxiety and lower QOL. RESULTS The baseline scores on the QOL instruments and anxiety questionnaire indicate poor organ-specific and general QOL as well as high levels of anxiety. Time since transplant was predictive of lower QOL as measured by Skindex-16 (p<.01). While not significant, number of NMSCs correlated with higher anxiety as measured by the STAI (p=.055). CONCLUSIONS While transplant patients enjoy longer survival, the quality of the extended life has room for improvement. Future studies will determine how QOL changes over time as these patients develop more numerous and aggressive skin cancers. Intervention with regular screening may not only lessen morbidity associated with skin cancer but may improve overall QOL in the posttransplant period.
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Affiliation(s)
- Fiona O'Reilly
- Department of Dermatology, Vanderbilt University, Nashville, Tennessee, USA
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Dolganiuc A, Garcia C, Kodys K, Szabo G. Distinct toll-like receptor expression in monocytes and T cells in chronic HCV infection. World J Gastroenterol 2006; 12:1198-204. [PMID: 16534871 PMCID: PMC4124429 DOI: 10.3748/wjg.v12.i8.1198] [Citation(s) in RCA: 65] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: Hepatitis C virus often establishes chronic infections. Recent studies suggest that viral and bacterial infections are more common in HCV-infected patients compared to controls. Pathogens are recognized by Toll-like receptors (TLRs) to shape adaptive and innate immune responses.
METHODS: In this study, to assess the ability of HCV-infected host to recognize invading pathogens, we investigated Toll-like receptor expression in innate (monocytes) and adaptive (T cells) immune cells by real-time PCR.
RESULTS: We determined that RNA levels for TLRs 2, 6. 7, 8, 9 and 10 mRNA levels were upregulated in both monocytes and T cells in HCV-infected patients compared to controls. TLR4 was only upregulated in T lymphocytes, while TLR5 was selectively increased in monocytes of HCV-infected patients. MD-2, a TLR4 co-receptor, was increased in patients’ monocytes and T cells while CD14 and MyD88 were increased only in monocytes.
CONCLUSION: Our data reveal novel details on TLR expression that likely relates to innate recognition of pathogens and immune defense in HCV-infected individuals.
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Affiliation(s)
- Angela Dolganiuc
- University of Massachusetts Medical School, Department of Medicine, 364 Plantation Street, Worcester, MA 01605-2324, United States
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Harwood CA, Proby CM, McGregor JM, Sheaff MT, Leigh IM, Cerio R. Clinicopathologic features of skin cancer in organ transplant recipients: a retrospective case-control series. J Am Acad Dermatol 2006; 54:290-300. [PMID: 16443060 DOI: 10.1016/j.jaad.2005.10.049] [Citation(s) in RCA: 103] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2005] [Revised: 10/10/2005] [Accepted: 10/18/2005] [Indexed: 02/06/2023]
Abstract
BACKGROUND Non-melanoma skin cancers (NMSCs) are increased in organ transplant recipients, but transplant and immunocompetent squamous and basal cell carcinomas (SCCs, BCCs) have not been compared previously in a single-center study. OBJECTIVE To compare clinicopathologic features of transplant and immunocompetent NMSCs. METHODS Consecutive transplant NMSCs (60 SCCs, 100 BCCs) and immunocompetent NMSCs (40 SCCs, 125 BCCs) presenting between 1995-1997. RESULTS Transplant patients were 15 years younger at time of NMSC diagnosis compared with immunocompetent individuals, and transplant tumors were often more multiple and extracephalic. Spindle cell morphology was more common in transplant SCCs, a superficial component was more common in transplant BCCs, and histologic features of HPV infection were overrepresented in transplant tumors. Outcome was worse for transplant SCCs but not transplant BCCs. LIMITATIONS Histologic features required to identify HPV infection have not been validated. CONCLUSIONS These findings have direct implications for clinical care. The increased frequency and distribution of transplant NMSCs underscore the importance of whole-body surveillance. Transplant SCCs, particularly those with diffuse spindle cell change, may require more aggressive management, whereas transplant BCCs do not. Finally, our data support differences in the pathogenesis of transplant NMSC, which may influence future preventive and therapeutic strategies.
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Affiliation(s)
- Catherine A Harwood
- Centre for Cutaneous Research, Institute for Cell and Molecular Science, Bart's and the London Queen Mary's School of Medicine and Dentistry, University of London, London, United Kingdom.
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