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Toia F, Cajozzo M, Rosatti F, Di Lorenzo S, Rinaldi G, Mazzucco W, Cordova A. Effectiveness of clinical and instrumental follow-up for cutaneous melanoma. Surg Oncol 2022; 44:101821. [PMID: 35947885 DOI: 10.1016/j.suronc.2022.101821] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Revised: 07/05/2022] [Accepted: 07/24/2022] [Indexed: 10/16/2022]
Abstract
INTRODUCTION Follow-up guidelines for melanoma greatly differ in the methods of screening for recurrence, and timing and duration of the follow up, with many areas of controversy and a lack of general consensus. The aims of this study are to present our protocol and case series for follow up and to summarize and discuss current literature on melanoma follow-up guidelines/recommendations in different countries. METHODS We retrospectively reviewed 539 patients operated for melanoma between 2004 and 2013 at the same Institution. Data on the diagnostic role of the different clinical and instrumental detection methods were adjusted for sex, age at diagnosis, staging and evaluated by Fisher's exact test and multivariate analysis. Recommendations from the literature were summarized and discussed. RESULTS Local recurrences and second melanoma were always identified through physical examination, irrespectively of melanoma staging. Regional metastases were most often identified through physical examination and ultrasound, being more frequent in stage II and III, while distant metastases were most often identified through CT scans. Surveillance follow-up schedules vary significantly depending on country, physician specialty, and stage of disease, with a lack of evidence on the efficacy of the different schemes. Similarities and controversies in the different follow-up protocols are presented and discussed. CONCLUSION Our clinical series showed that physical examination is very powerful in identifying local recurrences and second melanomas. Physical examination and ultrasound are equally powerful in identifying regional metastases, and alternating them over time could allow to reduce the number of follow-up visits. CT scans, differently from chest x-ray, showed a high power in identifying distant metastases. Surveillance follow-up schedules in the literature vary significantly depending on country, physician specialty, and stage of disease, with a lack of evidence on the efficacy of the different schemes. Standard protocols are desirable for a better evaluation of results.
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Affiliation(s)
- Francesca Toia
- Plastic and Reconstructive Surgery, Department of Surgical Oncological and Oral Sciences (DICHIRONS), University of Palermo, Palermo, Italy
| | - Marta Cajozzo
- Plastic and Maxillofacial Surgery Department, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Fernando Rosatti
- Plastic and Reconstructive Surgery, Department of Surgical Oncological and Oral Sciences (DICHIRONS), University of Palermo, Palermo, Italy.
| | - Sara Di Lorenzo
- Plastic and Reconstructive Surgery, Department of Surgical Oncological and Oral Sciences (DICHIRONS), University of Palermo, Palermo, Italy
| | - Gaetana Rinaldi
- Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy
| | - Walter Mazzucco
- Department of Health Promotion, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
| | - Adriana Cordova
- Plastic and Reconstructive Surgery, Department of Surgical Oncological and Oral Sciences (DICHIRONS), University of Palermo, Palermo, Italy
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Risk Stratification and Clinical Characteristics of Patients with Late Recurrence of Melanoma (>10 Years). J Clin Med 2022; 11:jcm11072026. [PMID: 35407631 PMCID: PMC9000041 DOI: 10.3390/jcm11072026] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Revised: 03/29/2022] [Accepted: 04/02/2022] [Indexed: 02/06/2023] Open
Abstract
Background: Most patients with high-risk melanomas develop metastasis within the first few years after diagnosis. However, late recurrence of melanoma is seen in patients that metastasize more than 10 years after the primary diagnosis; a metastasis after 15 years is considered an ultra-late recurrence. It is critical to better understand the clinical and biological characteristics of this subset of melanoma patients in order to offer an individual treatment plan and prevent metastasis. Methods: We retrospectively analyzed melanoma patients with recurrence ≥10 years after a primary diagnosis documented between 1993 and 2012 at the skin cancer center of the University Medical Center Leipzig, Germany. We conducted a comprehensive review of the literature and compared the results with our data. Available archived primary melanoma tissue was investigated with a seven-marker immunohistochemical signature (immunoprint®) previously validated to reliably identify high-risk patients within stages IB-III. Results: Out of 36 analyzed patients, a third metastasized ultra-late (≥15 years). The mean age at initial diagnosis was 51 years, with women being diagnosed comparatively younger than men. The largest proportion of patients with late recurrence had primary melanomas located on the trunk. The immunoprint® signature of the available primary melanomas allowed the accurate prediction of a high risk. However, it is difficult to draw a definitive conclusion from the small number of cases that could be analyzed with immunoprint® (n = 2) in this study. Apart from the primary tumor characteristics, the laboratory values at time of metastasis, comorbidities and outcome are also shown. Conclusion: Late and ultra-late recurrent melanomas seem not to differ from melanomas in general, apart from a distinctly higher proportion of lower leg localizations in ultra-late recurrent melanomas. The immunoprint® signature may help to identify high-risk primary tumors at the time of initial diagnosis. However, apart from the risk profile of the primary tumor, it seems that individual immune surveillance can control residual tumor cells for more than a decade. Advanced age and increasing comorbidities may contribute to a disturbed immunological balance.
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Late Metastatic Melanoma after 25 Years: A Case Report and a Brief Literature Review. Case Rep Surg 2020; 2020:2938236. [PMID: 33178477 PMCID: PMC7647769 DOI: 10.1155/2020/2938236] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2020] [Revised: 10/03/2020] [Accepted: 10/19/2020] [Indexed: 12/24/2022] Open
Abstract
The incidence of cutaneous malignant melanoma has shown a drastic increase over recent decades, and approximately 70% of newly diagnosed melanoma are tumors with a Breslow thickness less or equal to 1 mm. In the literature, there are well-documented rare cases of late metastasis of thin melanoma, and given their growing incidence, it is expected in the future to see more cases of late recurrence. We present a case report of a metastatic cutaneous melanoma 25 years from diagnosis and a review of the literature. A 61-year-old female patient presented with a newly discovered asymptomatic nodule on her thigh. Her relevant past medical history included a completely excided lesion with Breslow 1.4 mm thickness in 1989 for which she was followed up according to the guidelines and subsequently declared cured after 10 years of surveillance. Fine-needle aspiration and cytological analysis of the lesion proved to be a subcutaneous localization of malignant melanoma. The lesion was completely excised, and the patient has remained disease free since her surgery. The aim of this case report is to emphasize that late metastasis remains uncommon but a definitive cure from melanoma cannot always be considered a disease-free interval of 10 years. Physicians should always be aware of previous melanoma diagnosis with newly discovered suspicious lesions. Better patient education could improve the detection of recurrence and secondary melanomas without any need for more frequent follow-up visits and a prolonged follow-up time.
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Sarac E, Wilhelmi J, Thomas I, Leiter U, Keim U, Eigentler TK, Garbe C, Amaral T. Late recurrence of melanoma after 10 years - Is the course of the disease different from early recurrences? J Eur Acad Dermatol Venereol 2019; 34:977-983. [PMID: 31758713 DOI: 10.1111/jdv.16106] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2019] [Accepted: 10/17/2019] [Indexed: 01/25/2023]
Abstract
BACKGROUND It is known that melanoma can metastasize and recur many years after the first diagnosis. Although predictive and prognostic factors for melanoma are well defined, there is still insufficient information about the factors affecting the recurrence period and the effect of the recurrence time to survival. OBJECTIVES This study investigates the course of melanoma to show prognostic factors comparing early and late recurrence patients. The main objective is to uncover the effect of the recurrence time on the progression of the disease. METHODS In this retrospective study, late recurrence (LR) was defined as melanoma recurrence 10 years after the first diagnosis and early recurrence (ER) was defined as recurrence within 10 years. Gender, age, localization of primary tumour, time to first metastasis, survival rates, histological subtype, stage, tumour thickness, invasion level, ulceration and regression of the primary melanoma were documented. Survival curves were evaluated using the Kaplan-Meier and compared with the log-rank test. Multivariate Cox proportional hazard models were used to identify significant independent prognostic factors for melanoma-specific survival (MSS). RESULTS A total of 1537 melanoma patients were analysed. Early metastasis was developed in 1438 patients (93.6%), and 99 patients (6.4%) developed late metastasis. Late recurrence patients were younger (P < 0.001) and had fewer ulcerated (P = 0.005), fewer head/neck localized (P = 0.009) and thinner (P < 0.001) melanomas than ER patients. The MSS time (mean ± SD) was nearly identical for LR (31 ± 4.4 months 95% CI [22.3-39.7]) and ER (32 ± 1.9 months [28.3-35.7]). Multivariate regression analysis revealed male gender (hazard ratio [HR = 1.4, P < 0.001), truncal tumour localization (HR = 1.7, P < 0.001), tumour thickness (HR = 1.4, P < 0.045) and ulceration (HR = 1.3, P < 0.008) as significant independent prognostic factors for MSS. CONCLUSION Although ER and LR patients are found to have different clinicopathologic features, the time of the first recurrence after diagnosis do not seem to have an effect on the survival.
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Affiliation(s)
- E Sarac
- Center for Dermatooncology, Department of Dermatology, Eberhard Karls University of Tuebingen, Tuebingen, Germany.,Department of Dermatology, Koc University Hospital, Istanbul, Turkey
| | - J Wilhelmi
- Center for Dermatooncology, Department of Dermatology, Eberhard Karls University of Tuebingen, Tuebingen, Germany
| | - I Thomas
- Center for Dermatooncology, Department of Dermatology, Eberhard Karls University of Tuebingen, Tuebingen, Germany
| | - U Leiter
- Center for Dermatooncology, Department of Dermatology, Eberhard Karls University of Tuebingen, Tuebingen, Germany
| | - U Keim
- Center for Dermatooncology, Department of Dermatology, Eberhard Karls University of Tuebingen, Tuebingen, Germany
| | - T K Eigentler
- Center for Dermatooncology, Department of Dermatology, Eberhard Karls University of Tuebingen, Tuebingen, Germany
| | - C Garbe
- Center for Dermatooncology, Department of Dermatology, Eberhard Karls University of Tuebingen, Tuebingen, Germany
| | - T Amaral
- Center for Dermatooncology, Department of Dermatology, Eberhard Karls University of Tuebingen, Tuebingen, Germany.,Portuguese Air Force, Health Care Direction, Lisbon, Portugal
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Time-dependent change in relapse sites of renal cell carcinoma after curative surgery. Clin Exp Metastasis 2018. [DOI: 10.1007/s10585-018-9883-0] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Evans EB, Lin SY. New insights into tumor dormancy: Targeting DNA repair pathways. World J Clin Oncol 2015; 6:80-88. [PMID: 26468441 PMCID: PMC4600194 DOI: 10.5306/wjco.v6.i5.80] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2015] [Revised: 07/02/2015] [Accepted: 07/27/2015] [Indexed: 02/06/2023] Open
Abstract
Over the past few decades, major strides have advanced the techniques for early detection and treatment of cancer. However, metastatic tumor growth still accounts for the majority of cancer-related deaths worldwide. In fact, breast cancers are notorious for relapsing years or decades after the initial clinical treatment, and this relapse can vary according to the type of breast cancer. In estrogen receptor-positive breast cancers, late tumor relapses frequently occur whereas relapses in estrogen receptor-negative cancers or triple negative tumors arise early resulting in a higher mortality risk. One of the main causes of metastasis is tumor dormancy in which cancer cells remain concealed, asymptomatic, and untraceable over a prolonged period of time. Under certain conditions, dormant cells can re-enter into the cell cycle and resume proliferation leading to recurrence. However, the molecular and cellular regulators underlying this transition remain poorly understood. To date, three mechanisms have been identified to trigger tumor dormancy including cellular, angiogenic, and immunologic dormancies. In addition, recent studies have suggested that DNA repair mechanisms may contribute to the survival of dormant cancer cells. In this article, we summarize the recent experimental and clinical evidence governing cancer dormancy. In addition, we will discuss the role of DNA repair mechanisms in promoting the survival of dormant cells. This information provides mechanistic insight to explain why recurrence occurs, and strategies that may enhance therapeutic approaches to prevent disease recurrence.
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Leiter U, Eigentler T, Garbe C. Follow-up in patients with low-risk cutaneous melanoma: is it worth it? Melanoma Manag 2014; 1:115-125. [PMID: 30190817 PMCID: PMC6094616 DOI: 10.2217/mmt.14.22] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Follow-up examinations in melanoma aim to detect recurrences or secondary melanomas in an early phase of development. Follow-up guidelines that have been developed in many European countries, the USA and Australia show varying recommendations and are controversial, especially in patients with melanomas of 1.0 mm tumor thickness or less. This group contains 50-70% of all melanoma patients and the majority is unlikely to develop recurrences. On the other hand, within this entity, subgroups at higher risk for recurrences can be defined who require a more intense follow-up. This article discusses recommendations for the frequency, duration and costs of follow-up in low-risk melanoma patients. Patient preferences are addressed and a risk-adapted follow-up scheme is proposed.
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Affiliation(s)
- Ulrike Leiter
- Center of Dermato-Oncology, Department of Dermatology, University of Tuebingen, Liebermeisterstr. 25, 72076 Tuebingen, Germany
| | - Thomas Eigentler
- Center of Dermato-Oncology, Department of Dermatology, University of Tuebingen, Liebermeisterstr. 25, 72076 Tuebingen, Germany
| | - Claus Garbe
- Center of Dermato-Oncology, Department of Dermatology, University of Tuebingen, Liebermeisterstr. 25, 72076 Tuebingen, Germany
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Abstract
CONTEXT Metastatic uveal melanoma recurrence after ≥10 years is not well studied in the clinical literature. This study describes the clinical characteristics and natural history of patients with delayed tumor recurrence. OBJECTIVE To describe the characteristics of patients with delayed systemic recurrence of uveal melanoma and the natural history of the disease after recurrence. EVIDENCE ACQUISITION This is a chart review of patients treated between 1994 and 2008 at The University of Texas, MD Anderson Cancer Center for uveal melanoma whose disease recurred ≥10 years after treatment of the primary tumor. RESULTS Of 463 patients treated for metastatic uveal melanoma, 305 developed systemic recurrence within 5 years from the time of diagnosis of primary melanoma, 97 developed systemic recurrences between 5 and 10 years, whereas 61 patients developed metastasis after ≥10 years. The interval between primary to first systemic metastasis was a significant independent predictor of survival time from first systemic metastasis. The median survival time for patients with delayed metastatic recurrence after ≥10 years was significantly longer than for patients who had intermediate or early systemic recurrence. Levels of lactate dehydrogenase, serum alkaline phosphatase, serum albumin, age, M-stage, and performance status at time of recurrence, as well as sex were also independent predictors of survival time from systemic recurrence. CONCLUSIONS Longer time interval between primary and first systemic metastasis is significantly correlated with prolonged survival. Patients who survive ≥10 years without tumor metastasis after treatment for primary uveal melanoma cannot be considered cured. Prognosis remains poor for patients with metastatic uveal melanoma.
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Wang SH, Lin SY. Tumor dormancy: potential therapeutic target in tumor recurrence and metastasis prevention. Exp Hematol Oncol 2013; 2:29. [PMID: 24502434 PMCID: PMC4176492 DOI: 10.1186/2162-3619-2-29] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2013] [Accepted: 10/12/2013] [Indexed: 12/14/2022] Open
Abstract
In past decades, cancer patient survival has been improved with earlier detection and advancements in therapy. However, many patients who exhibit no clinical symptoms after frontline therapy subsequently suffer, often many years later, aggressive tumor recurrence. Cancer recurrence represents a critical clinical challenge in effectively treating malignancies and for patients’ quality of life. Tumor cell dormancy may help to explain treatment resistance and recurrence or metastatic reactivation. Understanding the dormant stage of tumor cells may help in discovering ways to maintain the dormant state or permanently eliminate dormant residual disseminated tumor cells. Over the past decade, numerous studies indicate that various mechanisms of tumor dormancy exist, including cellular dormancy (quiescence), angiogenic dormancy, and immunologic dormancy. In this short review, we summarize recent experimental and clinical evidence for these three mechanisms and other possible tumor microenvironment mechanisms that may influence tumor dormancy.
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Affiliation(s)
| | - Shiaw-Yih Lin
- Department of Systems Biology, Unit 950, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd,, Houston, TX 77054, USA.
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10
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Faries MB, Steen S, Ye X, Sim M, Morton DL. Late recurrence in melanoma: clinical implications of lost dormancy. J Am Coll Surg 2013; 217:27-34; discussion 34-6. [PMID: 23643694 DOI: 10.1016/j.jamcollsurg.2013.03.007] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2013] [Revised: 03/02/2013] [Accepted: 03/08/2013] [Indexed: 10/26/2022]
Abstract
BACKGROUND For patients with melanoma, if there has been no recurrence of disease 10 years after initial treatment, additional disease is believed to be very unlikely. However, such late recurrences are known to occur. The frequency of this phenomenon and its clinical significance are not well characterized due to the difficulty in obtaining relevant data. We examined a large, mature, institutional database to evaluate late recurrence. STUDY DESIGN The late recurrence cohort was defined as having a disease-free interval of 10 or more years after potentially curative treatment and was compared with an early recurrence cohort recurring within 3 years. Actuarial late recurrence frequency and factors associated with late recurrence were examined. Post-recurrence overall and melanoma-specific survival and prognostic variables were analyzed. RESULTS Among all patients, 408 exhibited late recurrence (mean disease-free interval 15.7 years). For patients who received primary treatment at our institution with 10 or more years follow-up, 327 of 4,731 (6.9%) showed late recurrence. On an actuarial basis, late recurrence rates were 6.8% and 11.3% at 15 and 20 years, respectively, for those with no recurrence at 10 years. Late recurrence was associated with both tumor (thin, non-ulcerated, non-head/neck, node negative) and patient (younger age, less male predominant) characteristics. Multivariate analysis confirmed younger age, thinner and node negative tumors in the late recurrence group. Late recurrences were more likely to be distant, but were associated with better post-recurrence survival on univariate and multivariate analyses. CONCLUSIONS Late melanoma recurrence is not rare. It occurs more frequently in certain clinical groups and is associated with improved post-recurrence survival.
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Affiliation(s)
- Mark B Faries
- John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, CA 90404, USA.
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Salama AKS, de Rosa N, Scheri RP, Pruitt SK, Herndon JE, Marcello J, Tyler DS, Abernethy AP. Hazard-rate analysis and patterns of recurrence in early stage melanoma: moving towards a rationally designed surveillance strategy. PLoS One 2013; 8:e57665. [PMID: 23516415 PMCID: PMC3596369 DOI: 10.1371/journal.pone.0057665] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2012] [Accepted: 01/24/2013] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND While curable at early stages, few treatment options exist for advanced melanoma. Currently, no consensus exists regarding the optimal surveillance strategy for patients after resection. The objectives of this study were to identify patterns of metastatic recurrence, to determine the influence of metastatic site on survival, and to identify high-risk periods for recurrence. METHODS A retrospective review of the Duke Melanoma Database from 1970 to 2004 was conducted that focused on patients who were initially diagnosed without metastatic disease. The time to first recurrence was computed from the date of diagnosis, and the associated hazard function was examined to determine the peak risk period of recurrence. Metastatic sites were coded by the American Joint Committee on Cancer (AJCC) system including local skin, distant skin and nodes (M1a), lung (M1b), and other distant (M1c). RESULTS Of 11,615 patients initially diagnosed without metastatic disease, 4616 (40%) had at least one recurrence. Overall the risk of initial recurrence peaked at 12 months. The risk of initial recurrence at the local skin, distant skin, and nodes peaked at 8 months, and the risk at lung and other distant sites peaked at 24 months. Patients with a cutaneous or nodal recurrence had improved survival compared to other recurrence types. CONCLUSIONS The risk of developing recurrent melanoma peaked at one year, and the site of first recurrence had a significant impact on survival. Defining the timing and expected patterns of recurrence will be important in creating an optimized surveillance strategy for this patient population.
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Affiliation(s)
- April K. S. Salama
- Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America
- Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina, United States of America
| | - Nicole de Rosa
- Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina, United States of America
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States of America
| | - Randall P. Scheri
- Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina, United States of America
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States of America
| | - Scott K. Pruitt
- Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina, United States of America
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States of America
| | - James E. Herndon
- Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina, United States of America
- Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina, United States of America
| | - Jennifer Marcello
- Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina, United States of America
| | - Douglas S. Tyler
- Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina, United States of America
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States of America
| | - Amy P. Abernethy
- Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America
- * E-mail:
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Pulitzer M, Brady MS, Blochin E, Amin B, Teruya-Feldstein J. Anaplastic Large Cell Lymphoma: A Potential Pitfall in the Differential Diagnosis of Melanoma. Arch Pathol Lab Med 2013; 137:280-3. [DOI: 10.5858/arpa.2011-0532-cr] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
The diagnosis of metastatic melanoma can be complicated by absent characteristic cytology, melanin, or antigen expression in a suspect tumor, putting the pathologist at risk for incorrectly diagnosing recurrent melanoma while missing a second malignancy. We report a 69-year-old man with a history of acral melanoma, metastatic to inguinal nodes, presenting with an ipsilateral thigh nodule. Histology showed a proliferation of pleomorphic cells in the dermis and subcutis, suspicious for melanoma. S100, Melan-A, and HMB-45 immunohistochemistry were negative. However, microphthalmia-associated transcription factor and CD117 labeled the neoplasm, prompting consideration of a late metastatic melanoma with loss of antigen expression. Subsequent immunolabeling for CD4, CD43, and CD30 and clonal T-cell gene rearrangements enabled the correct diagnosis of cutaneous anaplastic large cell lymphoma. This case illustrates a pitfall in evaluating tumors in patients with known metastatic melanoma, and emphasizes the need for broad-spectrum immunohistochemistry in cases that are not clear-cut.
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Affiliation(s)
- Melissa Pulitzer
- From the Departments of Pathology (Drs Pulitzer, Blochin, and Teruya-Feldstein) and Surgery (Dr Brady), Memorial Sloan-Kettering Cancer Center, New York, New York; and the Department of Pathology (Dr Amin), Montefiore Medical Center, New York, New York
| | - Mary Sue Brady
- From the Departments of Pathology (Drs Pulitzer, Blochin, and Teruya-Feldstein) and Surgery (Dr Brady), Memorial Sloan-Kettering Cancer Center, New York, New York; and the Department of Pathology (Dr Amin), Montefiore Medical Center, New York, New York
| | - Elen Blochin
- From the Departments of Pathology (Drs Pulitzer, Blochin, and Teruya-Feldstein) and Surgery (Dr Brady), Memorial Sloan-Kettering Cancer Center, New York, New York; and the Department of Pathology (Dr Amin), Montefiore Medical Center, New York, New York
| | - Bijal Amin
- From the Departments of Pathology (Drs Pulitzer, Blochin, and Teruya-Feldstein) and Surgery (Dr Brady), Memorial Sloan-Kettering Cancer Center, New York, New York; and the Department of Pathology (Dr Amin), Montefiore Medical Center, New York, New York
| | - Julie Teruya-Feldstein
- From the Departments of Pathology (Drs Pulitzer, Blochin, and Teruya-Feldstein) and Surgery (Dr Brady), Memorial Sloan-Kettering Cancer Center, New York, New York; and the Department of Pathology (Dr Amin), Montefiore Medical Center, New York, New York
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Abstract
The immune system can identify and destroy nascent tumor cells in a process termed cancer immunosurveillance, which functions as an important defense against cancer. Recently, data obtained from numerous investigations in mouse models of cancer and in humans with cancer offer compelling evidence that particular innate and adaptive immune cell types, effector molecules, and pathways can sometimes collectively function as extrinsic tumor-suppressor mechanisms. However, the immune system can also promote tumor progression. Together, the dual host-protective and tumor-promoting actions of immunity are referred to as cancer immunoediting. In this review, we discuss the current experimental and human clinical data supporting a cancer immunoediting process that provide the fundamental basis for further study of immunity to cancer and for the rational design of immunotherapies against cancer.
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Affiliation(s)
- Matthew D Vesely
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA
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OTSU U, FUKUI N, IKI M, MORIWAKI S, KIYOKANE K. Case of cutaneous malignant melanoma surviving 16 years with late recurrence. J Dermatol 2009; 36:598-603. [DOI: 10.1111/j.1346-8138.2009.00719.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Abstract
The notion that the immune system might control the growth of tumors was suggested over 100 years ago by the eminent microbiologist Paul Ehrlich. This concept was refined and expanded by Burnet and Thomas 50 years later with their articulation of the "immune surveillance" hypothesis. In its simplest form, the immune surveillance hypothesis suggests that neoplasms arise spontaneously and express novel antigens that are recognized by the immune system, which either eliminates the tumors or restrains their growth. Within the eye, immune responses are controlled and sometimes profoundly inhibited - a condition known as immune privilege. Immune privilege in the eye is the result of a complex array of anatomical, physiological, and immunoregulatory mechanisms that prevent the induction and expression of many immune responses. Tumors arising in the eye would seem to have an advantage in evading immune surveillance due to ocular immune privilege. Uveal melanoma, the most common and malignant intraocular tumor in adults, not only benefits from the immune privilege of the eye but also has adopted many of the mechanisms that contribute to ocular immune privilege as a strategy for protecting uveal melanoma cells once they leave the sanctuary of the eye and are disseminated systemically in the form of metastases. Although the immune system possesses a battery of effector mechanisms designed to rid the body of neoplasms, tumors are capable of rapidly evolving and countering even the most sophisticated immunological effector mechanisms. To date, tumors seem to be winning this arms race, but an increased understanding of these mechanisms should provide insights for designing immunotherapy that was envisioned over half a century ago, but has failed to materialize to date.
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Affiliation(s)
- Jerry Y Niederkorn
- Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9057, USA.
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Teng MWL, Swann JB, Koebel CM, Schreiber RD, Smyth MJ. Immune-mediated dormancy: an equilibrium with cancer. J Leukoc Biol 2008; 84:988-93. [PMID: 18515327 DOI: 10.1189/jlb.1107774] [Citation(s) in RCA: 213] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
This brief review discusses the role of the immune system in tumor development, covering a history of cancer immunity and a summary of the concept of cancer immunoediting, including its three phases: elimination, equilibrium, and escape. The latter half of this review then focuses specifically on the equilibrium phase, making note of previous work, suggesting that immunity might maintain cancer in a dormant state, and concluding with a description of a tractable mouse model unequivocally demonstrating that immunity can indeed hold preformed cancer in check. These findings form a framework for future studies aimed at validating immune-mediated cancer dormancy in humans with the hopes of devising new, immunotherapeutic strategies to treat established cancer.
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Clezardin P, Teti A. Bone metastasis: pathogenesis and therapeutic implications. Clin Exp Metastasis 2007; 24:599-608. [DOI: 10.1007/s10585-007-9112-8] [Citation(s) in RCA: 105] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2007] [Accepted: 10/01/2007] [Indexed: 12/20/2022]
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19
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Abstract
The ability of the immune system to identify and destroy nascent tumors, and to thereby function as a primary defense against cancer, has been debated for many decades. Recent findings by a number of investigators in both mouse models of cancer and humans with cancer now offer compelling evidence that particular immune cell types, effector molecules, and pathways can sometimes collectively function as extrinsic tumor suppressor mechanisms. This work provides the basis for further study of natural immunity to cancer and for rational use of this information in the design of immunotherapies in combination with other conventional cancer treatments.
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Affiliation(s)
- Jeremy B Swann
- Cancer Immunology Program, Peter MacCallum Cancer Centre, East Melbourne 8006, Victoria, Australia
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20
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Affiliation(s)
- Zafer Ozsoy
- Department of Plastic & Reconstructive Surgery, Vakif Gureba Education Hospital, Istanbul, Turkey.
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21
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Ultralate Metastasis of Cutaneous Melanoma. Dermatol Surg 2006. [DOI: 10.1097/00042728-200610000-00013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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22
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Pop LM, Smallshaw JE, Tucker TF, Stevenson FK, Vitetta ES. Failure of vaccination with idiotypic protein or DNA, (+/-IL-2), the depletion of regulatory T cells, or the blockade of CTLA-4 to prolong dormancy in mice with BCL1 lymphoma. J Immunother 2006; 28:525-34. [PMID: 16224269 DOI: 10.1097/01.cji.0000175493.05852.5a] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Immunization of mice with the idiotype (Id) immunoglobulin from the murine B cell lymphoma, BCL1, before inoculating tumor cells can induce tumor dormancy. In this model, the tumor cells grow for a short period of time and then regress. The mice live for months or years with approximately 1 million tumor cells in their spleens. Some mice relapse due to decreases in the anti-Id antibody titers or the development of mutations in the residual tumor cells which render them refractory to negative signaling by the anti-Id antibody. In this study we determined whether we could eliminate the residual dormant cells by using a DNA vaccine against the Id or by immunomodulation of T-cell subsets in vivo. Our results demonstrate that dormancy can be maintained by further immunizations with either the BCL1 Id protein or DNA vaccine encoding its single-chain Fv fragment. We also found that a cytotoxic T-cell response was not induced by either in vivo administration of vaccine alone or by the vaccine plus interleukin-2. In addition the injection of anti-cytotoxic T-lymphocyte-associate antigen did not prolong dormancy. Finally, the in vivo administration of anti-CD25 to deplete regulatory T cells did not prolong dormancy. Dormancy in this model is dependent primarily upon anti-Id antibodies, our results suggest that other strategies to target residual dormant BCL1 cells are warranted. They also suggest that the elimination of dormant tumor may represent a greater challenge than the elimination of primary tumors.
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MESH Headings
- Animals
- Antigens, CD
- Antigens, Differentiation/immunology
- CTLA-4 Antigen
- Cell Line
- Cyclin D1/therapeutic use
- Immunoglobulin Idiotypes/immunology
- Immunoglobulin Idiotypes/therapeutic use
- Immunotherapy, Active
- Interleukin-2/pharmacology
- Lymphoma, B-Cell/immunology
- Lymphoma, B-Cell/pathology
- Lymphoma, B-Cell/therapy
- Male
- Mice
- Mice, Inbred BALB C
- Neoplasm Transplantation
- Receptors, Interleukin-2/immunology
- Spleen/cytology
- T-Lymphocytes, Regulatory/immunology
- Vaccines, DNA/therapeutic use
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Affiliation(s)
- Laurentiu M Pop
- Cancer Immunobiology Center, University of Texas Southwestern Medical Center at Dallas, Texas 75390-8576, USA, and Cancer Sciences Division, Southampton University Hospitals, UK
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23
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Meng S, Tripathy D, Frenkel EP, Shete S, Naftalis EZ, Huth JF, Beitsch PD, Leitch M, Hoover S, Euhus D, Haley B, Morrison L, Fleming TP, Herlyn D, Terstappen LWMM, Fehm T, Tucker TF, Lane N, Wang J, Uhr JW. Circulating tumor cells in patients with breast cancer dormancy. Clin Cancer Res 2005; 10:8152-62. [PMID: 15623589 DOI: 10.1158/1078-0432.ccr-04-1110] [Citation(s) in RCA: 725] [Impact Index Per Article: 36.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
PURPOSE The purpose of this study was to test the hypothesis that circulating tumor cells (CTCs) are present in patients many years after mastectomy without evidence of disease and that these CTCs are shed from persisting tumor in patients with breast cancer dormancy. EXPERIMENTAL DESIGN We searched for CTCs in 36 dormancy candidate patients and 26 age-matched controls using stringent criteria for cytomorphology, immunophenotype, and aneusomy. RESULTS Thirteen of 36 dormancy candidates, 7 to 22 years after mastectomy and without evidence of clinical disease, had CTCs, usually on more than one occasion. Only 1 of 26 controls had a possible CTC (no aneusomy). The statistical difference of these two distributions was significant (exact P = 0.0043). The CTCs in patients whose primary breast cancer was just removed had a half-life measured in 1 to 2.4 hours. CONCLUSIONS The CTCs that are dying must be replenished every few hours by replicating tumor cells somewhere in the tissues. Hence, there appears to be a balance between tumor replication and cell death for as long as 22 years in dormancy candidates. We conclude that this is one mechanism underlying tumor dormancy.
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Affiliation(s)
- Songdong Meng
- Cancer Immunobiology Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390-8576, USA
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24
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Francken AB, Bastiaannet E, Hoekstra HJ. Follow-up in patients with localised primary cutaneous melanoma. Lancet Oncol 2005; 6:608-21. [PMID: 16054572 DOI: 10.1016/s1470-2045(05)70283-7] [Citation(s) in RCA: 136] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Follow-up services for patients with localised cutaneous melanoma are widely discussed but there is no international consensus. Our aim was to discuss frequency and duration of follow-up, type of health professional involved, optimum intensity of routine investigation, and patients' satisfaction with follow-up. Searches of the published work were directed at publications between January, 1985, and February, 2004 on recurrences, subsequent primary melanoma, routine tests, and patients' satisfaction. In a selection of 72 articles, 2142 (6.6%) recurrences were reported, 62% of which were detected by the patients themselves. 2.6% of patients developed a subsequent primary melanoma. Most investigators do not support high-intensity routine follow-up investigations. Of the various follow-up investigations requested by physicians, only medical history and physical examination seem to be cost effective. Lymph-node sonography seems to be a promising method for detection, although survival benefit remains to be proven. Patients were found to be anxious about follow-up visits, although other research showed that provision of information to patients was much appreciated. Published work on the follow-up of patients with cutaneous melanoma has mainly been retrospective and descriptive. Recommendations can be given with only a low grade of evidence. For meaningful guidelines to be developed, prospective, high-quality methodological research is needed.
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Affiliation(s)
- Anne Brecht Francken
- Division of Surgical Oncology, University of Groningen, University Medical Centre Groningen, Groningen, Netherlands
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25
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Affiliation(s)
- D J Eedy
- Department of Dermatology, Craigavon Area Hospital Group Trust, 68 Lurgan Road, Portadown BT63 5QQ, U.K.
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26
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Abstract
Tumour architecture mimics many of the features of normal tissues, with a cellular hierarchy that regulates the balance between cell renewal and cell death. Although many tumours contain cells with the characteristics of stem cells, the identity of the normal cells that acquire the first genetic hits leading to initiation of carcinogenesis has remained elusive. Identification of the primary cell of origin of cancers and the mechanisms that influence cell-fate decisions will be crucial for the development of novel non-toxic therapies that influence tumour-cell behaviour.
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Affiliation(s)
- Jesus Perez-Losada
- UCSF Comprehensive Cancer Center, 2340 Sutter Street, San Francisco, California 94143, USA.
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27
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28
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Abstract
A B cell lymphoma model of dormancy in mice was established by prior immunization to the B cell membrane immunoglobulin idiotype. The antibody to the idiotype was the major factor in inducing and maintaining dormancy and acted primarily as an agonist rather than via effector functions. CD8+ T cells synergized with anti-Id in inducing dormancy by secreting IFN-gamma. Cycling in the dormant population was reduced 3-5 fold, but each mouse contained approximately 10(6) tumor cells in its spleen, some of which were cycling, during the 1.5 years of observation. Thus, replication is balanced by cell death.
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Affiliation(s)
- J W Uhr
- Cancer Immunobiology Center, Department of Microbiology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390, USA.
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29
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Rubio N, Villacampa MM, El Hilali N, Blanco J. Metastatic burden in nude mice organs measured using prostate tumor PC-3 cells expressing the luciferase gene as a quantifiable tumor cell marker. Prostate 2000; 44:133-43. [PMID: 10881023 DOI: 10.1002/1097-0045(20000701)44:2<133::aid-pros6>3.0.co;2-n] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
BACKGROUND Sensitive procedures for quantitative measurement of tumor cell spread as a function of time and primary tumor size are necessary to generate models of metastasis and formulate therapies. METHODS Prostate carcinoma cells PC-3.luc expressing the luciferase gene were intramuscularly inoculated in nude mice to generate experimental tumors. Metastatic cells in target organs were easily counted by their capacity to produce light. RESULTS Tumor cells were very mobile and migrated to all the target organs examined: lymph nodes, brain, bone, lungs, liver, kidney, spleen, testicles, prostate, seminal vesicle, and scrotum. Organ colonization started very early, 14 days after inoculation, when primary tumors were very small and produced an amount of light equivalent to that generated by 2 x 10(4) tumor cells in vitro (tumor cell equivalents, TCEs). Tumor cell burden could be quantitatively described by power functions of time or primary tumor light-producing capacity. The ratio of metastatic TCEs to primary tumor TCEs clustered around organ characteristic values: 10(-3) for femur and lumbar lymph nodes, 10(-6) for the spleen, and 10(-3) for the added set of organs. CONCLUSIONS Dispersal of PC-3 tumor cells from IM experimental tumors started early before the third week postinoculation and when primary tumors had 2 x 10(4) TCEs. Tumor cells were found widely spread in all the organs tested. The possibility of easily quantifying tumor cell burden should make this approach useful for the study of metastasis and the development of antimetastatic therapies.
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Affiliation(s)
- N Rubio
- Department of Cell Biology, Institut de Recerca Oncològica, Barcelona, Spain
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30
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O'Sullivan GC. A cure for cancer? Dealing with minimal residual disease. Ir J Med Sci 2000; 169:13-6. [PMID: 10846849 DOI: 10.1007/bf03170474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Affiliation(s)
- G C O'Sullivan
- Department of Surgery, Mercy Hospital, University College Cork
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31
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Hsueh RC, Hammill AK, Marches R, Uhr JW, Scheuermann RH. Antigen receptor signaling induces differential tyrosine kinase activation and population stability in B-cell lymphoma. Curr Top Microbiol Immunol 1999; 246:299-304; discussion 305. [PMID: 10396069 DOI: 10.1007/978-3-642-60162-0_37] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Affiliation(s)
- R C Hsueh
- Department of Pathology, University of Texas Southwestern Medical Center, Dallas 75235-9072, USA
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32
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Abstract
Tumour latency, or dormancy, is a well-recognized clinical phenomenon and induction or maintenance of this state would appear to offer a novel therapeutic approach to limiting the effects of neoplastic disease. Current interest has focused on the role that neovascularization plays in this process and the consequences of shifts in the balance between angiogenic and anti-angiogenic peptides. Targeting tumour vasculature by the administration or induction of such anti-angiogenic peptides is close to clinical evaluation.
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Affiliation(s)
- I R Hart
- Richard Dimbleby Department of Cancer Research/Imperial Cancer Research Fund, Rayne Institute, St Thomas' Hospital, London, U.K.
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33
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Racila E, Euhus D, Weiss AJ, Rao C, McConnell J, Terstappen LW, Uhr JW. Detection and characterization of carcinoma cells in the blood. Proc Natl Acad Sci U S A 1998; 95:4589-94. [PMID: 9539782 PMCID: PMC22534 DOI: 10.1073/pnas.95.8.4589] [Citation(s) in RCA: 509] [Impact Index Per Article: 18.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/03/1998] [Indexed: 02/07/2023] Open
Abstract
A highly sensitive assay combining immunomagnetic enrichment with multiparameter flow cytometric and immunocytochemical analysis has been developed to detect, enumerate, and characterize carcinoma cells in the blood. The assay can detect one epithelial cell or less in 1 ml of blood. Peripheral blood (10-20 ml) from 30 patients with carcinoma of the breast, from 3 patients with prostate cancer, and from 13 controls was examined by flow cytometry for the presence of circulating epithelial cells defined as nucleic acid+, CD45(-), and cytokeratin+. Highly significant differences in the number of circulating epithelial cells were found between normal controls and patients with cancer including 17 with organ-confined disease. To determine whether the circulating epithelial cells in the cancer patients were neoplastic cells, cytospin preparations were made after immunomagnetic enrichment and were analyzed. Epithelial cells from patients with breast cancer generally stained with mAbs against cytokeratin and 3 of 5 for mucin-1. In contrast, no cells that stained for these antigens were observed in the blood from normal controls. The morphology of the stained cells was consistent with that of neoplastic cells. Of 8 patients with breast cancer followed for 1-10 months, there was a good correlation between changes in the level of tumor cells in the blood with both treatment with chemotherapy and clinical status. The present assay may be helpful in early detection, in monitoring disease, and in prognostication.
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Affiliation(s)
- E Racila
- Cancer Immunobiology Center, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75235, USA
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34
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Keller H, Hacker R, Stolte M. [Simultaneous enucleation of a pulmonary melanoma metastasis and myocardial revascularization]. MEDIZINISCHE KLINIK (MUNICH, GERMANY : 1983) 1997; 92:683-5. [PMID: 9480400 DOI: 10.1007/bf03044826] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND The incidence of late, recurrence of malignant melanoma, is a well known, but very rare clinical experience. CASE REPORT We report a case of simultaneous myocardial revascularisation and resection of pulmonary melanoma metastasis. In 1963 an enucleation of the right eye was necessary due to an ocular melanoma. In 1993 the patient suffered acute left heart failure and a 3-vessel disease with severe reduced left ventricular function was diagnosed. Chest X-ray examination revealed a singular pulmonary lesion in the right lower lobe with a diameter of 5.5 cm. Myocardial revascularisation and resection of the pulmonary focus was performed simultaneously without complication. The histological examination documented a pulmonary late recurrence of malignant melanoma. Up to this time (3 years later) the patient is free of cardiac symptoms and there is no evidence of further late recurrence of malignant melanoma. CONCLUSION The appreciable number of patients who, after a disease-free interval of 10 to 20 years, develop a late recurrence of a malignant melanoma, and in particular-as in the present case-a choroidal melanoma, is powerful evidence for a need to keep these patients under lifelong surveillance.
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Affiliation(s)
- H Keller
- Innere Abteilung, Kreiskankenhauses Rastatt
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35
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Needle MN, Rorke LB, Winkler P. Late recurrence of a brain tumor. MEDICAL AND PEDIATRIC ONCOLOGY 1997; 29:67-71. [PMID: 9142210 DOI: 10.1002/(sici)1096-911x(199707)29:1<67::aid-mpo13>3.0.co;2-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Affiliation(s)
- M N Needle
- Division of Pediatric Neuro-Oncology, Children's Hospital of Philadelphia, Pennsylvania, USA
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36
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37
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Uhr JW, Scheuermann RH, Street NE, Vitetta ES. Cancer dormancy: opportunities for new therapeutic approaches. Nat Med 1997; 3:505-9. [PMID: 9142117 DOI: 10.1038/nm0597-505] [Citation(s) in RCA: 130] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Affiliation(s)
- J W Uhr
- Cancer Immunobiology Center, University of Texas Southwestern Medical Center at Dallas 75235, USA
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38
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Tincani AJ, Martins AS, Lage HDT, Souza LS. Melanoma ganglionic metastasis 30 years after treatment of the primary tumor--a case report. SAO PAULO MED J 1996; 114:1131-3. [PMID: 9077023 DOI: 10.1590/s1516-31801996000200005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
The recurrence of melanoma in patients is well-documented, and is dependent on a number of factors. We report a case in which a patient had a case of ganglionar metastasis in the neck after a 30-year disease-free interval following primary treatment.
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Affiliation(s)
- A J Tincani
- Department of Surgery, School for Medical Science, State University of Campinas (UNICAMP), Brazil
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39
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Abstract
Recurrent melanoma occurs in approximately one third of patients treated for cutaneous melanoma. Although the majority of recurrence occurs within the first few years of primary therapy, a significant number remains at risk beyond 10 years. With rising incidence of recurrent melanoma in Western countries, physicians will undoubtedly face the challenge of managing these patients with the limited therapeutic options currently available. Once melanoma has recurred, the overall prognosis is poor. Localized disease is best treated with complete resection, if indicated. Our existing armamentarium for systemic treatment falls short of altering the course of natural history of melanoma, but regional chemotherapy is an effective modality for in-transit disease and satellitosis. Translational research in molecular genetics and immunology will fuel new ideas for the design of rational strategies toward tumor eradication. Ongoing trials that use gene-modified melanoma cells have begun a new chapter in cancer therapeutics and lend us a closer examination of bench-top science at the bedside.
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Affiliation(s)
- R S Yeung
- Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania
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40
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Abstract
BACKGROUND Melanoma may remain clinically dormant for years, and patients may have distant metastatic disease decades after the initial diagnosis is made. Because of this potential for late recurrence, the concept of "cure" for melanoma is not particularly meaningful. METHODS To understand better the risks of future disease as a function of time elapsed after diagnosis, the clinical course of melanoma was reviewed in 5838 patients. Using conditional probability methods, the risk of recurrent disease and the risk of death were determined for 1-year and 5-year intervals during the first 15 years of follow-up. RESULTS The estimated 5-year risk of recurrence declined from 44% at the time of diagnosis to 21% after 6 years. The 5-year risk of mortality decreased from 26% after 1 year to 16% after 9 years. Among patients with recurrent or metastatic disease, the annual risk of mortality was approximately 20% per year for 3 years; thereafter, the risk declined markedly. Among patients with thick primary lesions, the greatest risk was during the first few years after diagnosis, but in patients with thin lesions, the risk was distributed evenly over 15 years and did not decrease with time. CONCLUSIONS Conditional probability methods permit estimation of future risks to address questions frequently asked by patients with cancer who want to know when they can be considered cured of cancer or when the risk of recurrent disease has decreased. These data on the future risk of recurrent disease and mortality can give a patient meaningful information on which to base life decisions.
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Affiliation(s)
- C L Slingluff
- Department of Surgery, Duke University Medical Center, Durham, North Carolina
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41
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Abstract
Through the UCLA tumor registry, patients treated for late-relapse malignant melanoma (after a 10-year disease-free interval) were identified and studied retrospectively. The patients were studied in regards to age, sex, primary site of the lesion, the disease-free interval, elective lymph node dissection, mode of recurrence and survival time following relapse. The histologic characteristics studied included the maximal tumor thickness, Clark's levels, rate of mitoses, and presence of ulceration. Based on the 0.84% incidence of late-relapse, the recommendation for annual life-time follow-up examinations for all patients with malignant melanoma is supported.
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Affiliation(s)
- D P Tahery
- UCLA Division of Dermatology, Veterans Administration Wadsworth West Los Angeles Medical Center, California
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42
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Shaw HM, Rivers JK, McCarthy SW, McCarthy WH. Cutaneous melanomas exhibiting unusual biologic behavior. World J Surg 1992; 16:196-202. [PMID: 1561799 DOI: 10.1007/bf02071521] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
In rare instances, primary malignant melanoma thickness fails to predict the biologic course of the disease: lesions less than 0.8 mm thick may recur locally or metastasize, lesions greater than 5.5 mm thick may not prove to be fatal within the expected interval of time, and melanoma recurrences may develop greater than 10 years after first definitive melanoma treatment. The large Sydney Melanoma Unit data base of over 9,500 patients treated over a 41-year period provided a unique opportunity to study the characteristics and prognosis of these patients with unusual melanomas. In stage I patients with thin lesions, and no sign of disease elsewhere, presence of ulceration, high mitotic activity, and/or penetration into the reticular dermis predisposed these melanomas to recur and regression did not emerge as a risk factor for recurrence. This was in sharp contrast to the histology of the thin lesions in patients with concurrent regional lymph node metastases (stage II). Moderate to severe regression was present in all the latter lesions, ulceration and mitoses were absent, and none penetrated beyond the papillary dermis. No specific criteria were found that could identify those stage I or II patients with thick melanomas but at low risk for recurrence or those patients with localized disease (stage I) who required long-term follow-up beyond 10 years. These results indicate that guidelines for follow-up of melanoma patients after first definitive treatment may not be appropriate for a small proportion of patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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Affiliation(s)
- H M Shaw
- Sydney Melanoma Unit, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
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43
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Lees VC, Briggs JC. Effect of initial biopsy procedure on prognosis in Stage 1 invasive cutaneous malignant melanoma: review of 1086 patients. Br J Surg 1991; 78:1108-10. [PMID: 1933198 DOI: 10.1002/bjs.1800780923] [Citation(s) in RCA: 69] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
After treatment for primary clinical Stage 1 invasive cutaneous malignant melanoma, 1086 patients were followed for a minimum of 5 years from initial operation. Patient data were retrieved from the unit's melanoma registry; 96 (8.8 per cent) were treated initially by incisional biopsy, 292 (26.9 per cent) by narrow margin excision biopsy and 698 (64.3 per cent) by wide margin excision. Logistic regression analysis was performed to assess the statistical significance of the association between the various factors. The method of initial biopsy was related to maximal tumour thickness, age, and sex. Incisional biopsy rendered 38 out of 96 (40 per cent) lesions not fully assessable on current histopathological criteria, significantly higher than for the other biopsy techniques (P less than 0.0001). Incisional biopsy did not adversely affect prognosis in terms of local recurrence and mortality. Prognosis was related to tumour thickness, age and sex of the patient, and not to biopsy technique. We recommend that all suspicious lesions should be submitted to excisional rather than incisional biopsy to avoid compromising the histological assessment, given the importance of maximal tumour thickness in determining treatment and prognosis.
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Affiliation(s)
- V C Lees
- Department of Plastic Surgery, Addenbrooke's Hospital, Cambridge, UK
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44
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Abstract
Analysis of 7104 patients with melanoma seen at Duke University identified 168 who experienced their first recurrence 10 or more years after diagnosis, for an incidence of 2.4%. This included patients with all stages of disease. There was no sex, age, or primary site predominance. The mean disease-free interval for cutaneous melanomas was 14.3 years versus 22.3 years for ocular primary melanomas. The prognosis following relapse was related to the site of recurrence. Survival after local or regional node recurrence was often prolonged; survival after distant metastases was usually limited. Patients with ocular primaries had the highest incidence of distant metastases, and the shortest subsequent survival. An additional 483 patients were identified who survived 10 or more years without evidence of recurrence; of these 651 patients with long disease-free intervals, 25% (168 of 651) developed recurrent disease. This demonstrates that a 10-year disease-free interval cannot be considered a cure, and emphasizes the importance of continued annual follow-up.
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Affiliation(s)
- N J Crowley
- Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710
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