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Fulminant Disseminated Intravascular Coagulation as Initial Presentation of BRAF-Mutated Melanoma

Fulminant Disseminated Intravascular Coagulation as Initial Presentation of BRAF-Mutated Melanoma Hindawi Case Reports in Oncological Medicine Volume 2019, Article ID 9246596, 2 pages https://doi.org/10.1155/2019/9246596 Case Report Fulminant Disseminated Intravascular Coagulation as Initial Presentation of BRAF-Mutated Melanoma 1 2 2,3 3 2 Jeremy Chuang , An Uche, Rohan Gupta, Kim Margolin, and Phyllis Kim Department of Internal Medicine, Harbor-UCLA Medical Center, 1000 West Carson Street, Torrance, CA 90509, USA Division of Hematology and Medical Oncology, Harbor-UCLA Medical Center, 1000 West Carson Street, Torrance, CA 90509, USA Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, 1500 E Duarte Rd, Duarte, CA 91010, USA Correspondence should be addressed to Jeremy Chuang; jchuang@dhs.lacounty.gov Received 6 January 2019; Accepted 27 March 2019; Published 9 April 2019 Academic Editor: Raffaele Palmirotta Copyright © 2019 Jeremy Chuang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Acute disseminated intravascular coagulation (DIC) is a pathological process involving dysfunction of the coagulation cascade. In this case report, we discuss a 33-year-old woman with BRAF V600E-mutated metastatic melanoma who presented in fulminant DIC with concurrent hemorrhagic and thrombotic manifestations and discuss the patient’s brief response to combination therapy. In our discussion, we highlight the current understanding of DIC and also identify opportunities for future research to elucidate the genetic aberrations in melanoma that may result in treatment resistance to combination therapy. AST 35 U/L, ALT 17 U/L, total bilirubin 1.1 mg/dL, and 1. Introduction LDH 615 U/L. Computerized tomography scans showed Acute disseminated intravascular coagulation (DIC) is an multiple small pulmonary nodules, small bowel dilatation, a infrequent presenting syndrome of solid tumors. Herein, 6.8 cm left pelvic mass associated with peritoneal caking, we discuss a 33-year-old woman with BRAF V600E- and lympadenopahy in the neck, central mesentery, and mutated metastatic melanoma who presented in fulminant inguinofemoral chain. DIC with concurrent hemorrhagic and thrombotic manifes- The patient underwent emergency laparotomy for a tations and only a brief response to combination BRAF and hemoperitoneum and small bowel intussusception secondary MEK inhibition. to a small bowel metastasis of melanoma (later determined to have BRAF v600E mutation). On postoperative day 3, she developed dusky discoloration of the nose and several digits 2. Case Report and was treated with unfractionated intravenous heparin. Her course was further complicated by intra-abdominal A 33-year-old Caucasian woman presented with one day of hematochezia and hematemesis and an enlarging left lower hematoma, necrotic bowel secondary to microthrombi quadrant inguinal mass over the prior six months. She had requiring resection, extensive limb necrosis requiring ampu- tations, and acute tubular necrosis requiring hemodialysis. a 9×9cm tender mass in the left inguinal region and a dif- fusely tender abdomen. Initial laboratory tests showed hemo- A primary cutaneous melanoma was not identified. The patient received dabrafenib and trametinib and experienced globin 9.9 g/dL, platelets 154K/cumm, INR 3.51, PT 35.5 seconds, PTT 35.4 seconds, serum fibrinogen < 30 mg/dL, prompt resolution of DIC and improvement of renal elevated D dimer, and serum lactate 3.9 mmol/L. Serum function. Unfortunately, control of malignancy was brief (<4 weeks), and she died of disease without recurrent DIC. creatinine was 0.96 mg/dL, alkaline phosphatase 51 U/L, 2 Case Reports in Oncological Medicine Table 1: Case reports of metastatic melanoma presenting with DIC. Source Clinical presentation Diagnosis Treatment course Citation 62-year-old woman presenting with hematuria and DIC 2 months after BRAF-mutated metastatic Bhattacharyya et al. DIC improved with vemurafenib. [1] she was diagnosed with BRAF- melanoma mutated metastatic melanoma. 61-year-old woman with history of Dacarbazine was started; however, metastatic melanoma presenting Lepelley-Dupont et al. Metastatic melanoma patient expired secondary to [2] with acute hemorrhagic shock with hemorrhagic shock. evidence of DIC. 37-year-old man with history of excised melanoma 6 years ago found DIC resolved with dacarbazine, Schlaeppi et al. Metastatic melanoma [3] to have diffuse metastatic disease of vinblastine, and cisplatine. the liver and DIC. 3. Discussion coagulation in a patient with metastatic melanoma,” Oncology Research and Treatment, vol. 29, no. 11, pp. 531–533, 2006. Although several malignancies are associated with DIC, there [4] M. B. Donati, C. Gambacorti-Passerini, B. Casali et al., “Cancer are limited case reports of acute DIC as the initial presenta- procoagulant in human tumor cells: evidence from melanoma tion of metastatic melanoma (Table 1) [1–3]. Tissue factor, patients,” Cancer Research, vol. 46, 12, Part 1, pp. 6471–6474, a potent procoagulant, is generated by tumor cells and inflammatory cells as well as by tissue necrosis and endothe- [5] C. T. Esmon, “Possible involvement of cytokines in diffuse lial damage. Cancer procoagulant (CP), which directly acti- intravascular coagulation and thrombosis,” Best Practice & vates factor X, has been associated with metastatic Research Clinical Haematology, vol. 12, no. 3, pp. 343–359, melanoma cells [4]. Tumor necrosis factor, interleukin-6, and other malignancy-associated proinflammatory cytokines may also contribute [5]. In our patient, the triggers for DIC could have been tissue damage from widespread peritoneal metastases overexpressing TF/CP or highly aggressive tumor with increased cell turnover, which would be consistent with the remarkably brief period of disease control using com- bined MAP kinase inhibition. It is likely that this patient’s melanoma had from the outset a set of mutations or a pattern of gene expression associated with highly aggressive behav- ior, DIC, and resistance to mutation-targeted therapy. Conflicts of Interest The authors have no relevant conflicts of interest to disclose. Acknowledgments The research was conducted with support of the faculty at Harbor-UCLA Medical Center and City of Hope National Medical Center. References [1] A. Bhattacharyya, A. Cooper, A. Hong, H. Iland, and C. McNeil, “Successful management of life-threatening disseminated intra- vascular coagulopathy due to metastatic melanoma,” Internal medicine journal, vol. 44, no. 2, pp. 207-208, 2014. [2] C. Lepelley-Dupont, N. Meyer, T. Lesimple, P. Gueret, H. Adamski, and J. Chevrant-Breton, “Melanoma-associated disseminated intravascular coagulation,” Journal of the Euro- pean Academy of Dermatology and Venereology, vol. 23, no. 6, pp. 720-721, 2009. [3] M. R. Schlaeppi, W. Korte, R. . Moos, T. Cerny, and S. Gillessen, “Successful treatment of acute disseminated intravascular MEDIATORS of INFLAMMATION The Scientific Gastroenterology Journal of World Journal Research and Practice Diabetes Research Disease Markers Hindawi Hindawi Publishing Corporation Hindawi Hindawi Hindawi Hindawi www.hindawi.com Volume 2018 http://www www.hindawi.com .hindawi.com V Volume 2018 olume 2013 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 International Journal of Journal of Immunology Research Endocrinology Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 Submit your manuscripts at www.hindawi.com BioMed PPAR Research Research International Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 Journal of Obesity Evidence-Based Journal of Journal of Stem Cells Complementary and Ophthalmology International Alternative Medicine Oncology Hindawi Hindawi Hindawi Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2013 Parkinson’s Disease Computational and Behavioural Mathematical Methods AIDS Oxidative Medicine and in Medicine Neurology Research and Treatment Cellular Longevity Hindawi Hindawi Hindawi Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Case Reports in Oncological Medicine Hindawi Publishing Corporation

Fulminant Disseminated Intravascular Coagulation as Initial Presentation of BRAF-Mutated Melanoma

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Hindawi Publishing Corporation
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Copyright © 2019 Jeremy Chuang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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10.1155/2019/9246596
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Abstract

Hindawi Case Reports in Oncological Medicine Volume 2019, Article ID 9246596, 2 pages https://doi.org/10.1155/2019/9246596 Case Report Fulminant Disseminated Intravascular Coagulation as Initial Presentation of BRAF-Mutated Melanoma 1 2 2,3 3 2 Jeremy Chuang , An Uche, Rohan Gupta, Kim Margolin, and Phyllis Kim Department of Internal Medicine, Harbor-UCLA Medical Center, 1000 West Carson Street, Torrance, CA 90509, USA Division of Hematology and Medical Oncology, Harbor-UCLA Medical Center, 1000 West Carson Street, Torrance, CA 90509, USA Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, 1500 E Duarte Rd, Duarte, CA 91010, USA Correspondence should be addressed to Jeremy Chuang; jchuang@dhs.lacounty.gov Received 6 January 2019; Accepted 27 March 2019; Published 9 April 2019 Academic Editor: Raffaele Palmirotta Copyright © 2019 Jeremy Chuang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Acute disseminated intravascular coagulation (DIC) is a pathological process involving dysfunction of the coagulation cascade. In this case report, we discuss a 33-year-old woman with BRAF V600E-mutated metastatic melanoma who presented in fulminant DIC with concurrent hemorrhagic and thrombotic manifestations and discuss the patient’s brief response to combination therapy. In our discussion, we highlight the current understanding of DIC and also identify opportunities for future research to elucidate the genetic aberrations in melanoma that may result in treatment resistance to combination therapy. AST 35 U/L, ALT 17 U/L, total bilirubin 1.1 mg/dL, and 1. Introduction LDH 615 U/L. Computerized tomography scans showed Acute disseminated intravascular coagulation (DIC) is an multiple small pulmonary nodules, small bowel dilatation, a infrequent presenting syndrome of solid tumors. Herein, 6.8 cm left pelvic mass associated with peritoneal caking, we discuss a 33-year-old woman with BRAF V600E- and lympadenopahy in the neck, central mesentery, and mutated metastatic melanoma who presented in fulminant inguinofemoral chain. DIC with concurrent hemorrhagic and thrombotic manifes- The patient underwent emergency laparotomy for a tations and only a brief response to combination BRAF and hemoperitoneum and small bowel intussusception secondary MEK inhibition. to a small bowel metastasis of melanoma (later determined to have BRAF v600E mutation). On postoperative day 3, she developed dusky discoloration of the nose and several digits 2. Case Report and was treated with unfractionated intravenous heparin. Her course was further complicated by intra-abdominal A 33-year-old Caucasian woman presented with one day of hematochezia and hematemesis and an enlarging left lower hematoma, necrotic bowel secondary to microthrombi quadrant inguinal mass over the prior six months. She had requiring resection, extensive limb necrosis requiring ampu- tations, and acute tubular necrosis requiring hemodialysis. a 9×9cm tender mass in the left inguinal region and a dif- fusely tender abdomen. Initial laboratory tests showed hemo- A primary cutaneous melanoma was not identified. The patient received dabrafenib and trametinib and experienced globin 9.9 g/dL, platelets 154K/cumm, INR 3.51, PT 35.5 seconds, PTT 35.4 seconds, serum fibrinogen < 30 mg/dL, prompt resolution of DIC and improvement of renal elevated D dimer, and serum lactate 3.9 mmol/L. Serum function. Unfortunately, control of malignancy was brief (<4 weeks), and she died of disease without recurrent DIC. creatinine was 0.96 mg/dL, alkaline phosphatase 51 U/L, 2 Case Reports in Oncological Medicine Table 1: Case reports of metastatic melanoma presenting with DIC. Source Clinical presentation Diagnosis Treatment course Citation 62-year-old woman presenting with hematuria and DIC 2 months after BRAF-mutated metastatic Bhattacharyya et al. DIC improved with vemurafenib. [1] she was diagnosed with BRAF- melanoma mutated metastatic melanoma. 61-year-old woman with history of Dacarbazine was started; however, metastatic melanoma presenting Lepelley-Dupont et al. Metastatic melanoma patient expired secondary to [2] with acute hemorrhagic shock with hemorrhagic shock. evidence of DIC. 37-year-old man with history of excised melanoma 6 years ago found DIC resolved with dacarbazine, Schlaeppi et al. Metastatic melanoma [3] to have diffuse metastatic disease of vinblastine, and cisplatine. the liver and DIC. 3. Discussion coagulation in a patient with metastatic melanoma,” Oncology Research and Treatment, vol. 29, no. 11, pp. 531–533, 2006. Although several malignancies are associated with DIC, there [4] M. B. Donati, C. Gambacorti-Passerini, B. Casali et al., “Cancer are limited case reports of acute DIC as the initial presenta- procoagulant in human tumor cells: evidence from melanoma tion of metastatic melanoma (Table 1) [1–3]. Tissue factor, patients,” Cancer Research, vol. 46, 12, Part 1, pp. 6471–6474, a potent procoagulant, is generated by tumor cells and inflammatory cells as well as by tissue necrosis and endothe- [5] C. T. Esmon, “Possible involvement of cytokines in diffuse lial damage. Cancer procoagulant (CP), which directly acti- intravascular coagulation and thrombosis,” Best Practice & vates factor X, has been associated with metastatic Research Clinical Haematology, vol. 12, no. 3, pp. 343–359, melanoma cells [4]. Tumor necrosis factor, interleukin-6, and other malignancy-associated proinflammatory cytokines may also contribute [5]. In our patient, the triggers for DIC could have been tissue damage from widespread peritoneal metastases overexpressing TF/CP or highly aggressive tumor with increased cell turnover, which would be consistent with the remarkably brief period of disease control using com- bined MAP kinase inhibition. It is likely that this patient’s melanoma had from the outset a set of mutations or a pattern of gene expression associated with highly aggressive behav- ior, DIC, and resistance to mutation-targeted therapy. Conflicts of Interest The authors have no relevant conflicts of interest to disclose. Acknowledgments The research was conducted with support of the faculty at Harbor-UCLA Medical Center and City of Hope National Medical Center. References [1] A. Bhattacharyya, A. Cooper, A. Hong, H. Iland, and C. McNeil, “Successful management of life-threatening disseminated intra- vascular coagulopathy due to metastatic melanoma,” Internal medicine journal, vol. 44, no. 2, pp. 207-208, 2014. [2] C. Lepelley-Dupont, N. Meyer, T. Lesimple, P. Gueret, H. Adamski, and J. Chevrant-Breton, “Melanoma-associated disseminated intravascular coagulation,” Journal of the Euro- pean Academy of Dermatology and Venereology, vol. 23, no. 6, pp. 720-721, 2009. [3] M. R. Schlaeppi, W. Korte, R. . Moos, T. Cerny, and S. Gillessen, “Successful treatment of acute disseminated intravascular MEDIATORS of INFLAMMATION The Scientific Gastroenterology Journal of World Journal Research and Practice Diabetes Research Disease Markers Hindawi Hindawi Publishing Corporation Hindawi Hindawi Hindawi Hindawi www.hindawi.com Volume 2018 http://www www.hindawi.com .hindawi.com V Volume 2018 olume 2013 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 International Journal of Journal of Immunology Research Endocrinology Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 Submit your manuscripts at www.hindawi.com BioMed PPAR Research Research International Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 Journal of Obesity Evidence-Based Journal of Journal of Stem Cells Complementary and Ophthalmology International Alternative Medicine Oncology Hindawi Hindawi Hindawi Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2013 Parkinson’s Disease Computational and Behavioural Mathematical Methods AIDS Oxidative Medicine and in Medicine Neurology Research and Treatment Cellular Longevity Hindawi Hindawi Hindawi Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018

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