In this report we describe a case of a malignant cutaneous melanoma metastasizing to the pleural surface and peritoneal cavity 5 years after surgical resection of the primary lesion. Malignant cutaneous melanoma is a very aggressive cancer able to metastasize anywhere in the body. Pleural secondary lesions represent a rare event described only in a small number of patients and the association with peritoneal localizations may suggest an uncommon pattern of spread that we discuss. Free full text available at www.tumorionline.it

De Vita F.

Di Benedetto G.

Fabozzi A.

Fabozzi T.

Fasano M.

Fascione A.

Ferrara M.

Giordano G.

Guerrera B.

English

Archivio Istituzionale della Ricerca- Università degli Studi di Foggia

See discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/51085184Metastatic melanoma: An unusual presentationArticle  in  Tumori · January 2011DOI: 10.1700/611.7152 · Source: PubMedCITATIONS6READS3929 authors, including:Some of the authors of this publication are also working on these related projects:RAS , BRA mutation Test and Cytological Diagnosis with a Single Fine Needle Cytology Sample View projectNab Paclitaxel in metastatic pancreatic cancer: the Italian "real life" experience View projectFerdinando De VitaUniversità degli Studi della Campania "Luigi Vanvitelli215 PUBLICATIONS   4,938 CITATIONS   SEE PROFILEGuido GiordanoIRCCS Ospedale Casa Sollievo della Sofferenza39 PUBLICATIONS   144 CITATIONS   SEE PROFILEAlessio FabozziIstituto Oncologico Veneto34 PUBLICATIONS   353 CITATIONS   SEE PROFILEGiuseppe Di BenedettoAzienda Sanitaria Locale Caserta32 PUBLICATIONS   245 CITATIONS   SEE PROFILEAll content following this page was uploaded by Giuseppe Di Benedetto on 30 May 2014.The user has requested enhancement of the downloaded file.Key words: melanoma, pleuralmetastasis, peritoneal carcinosis.Correspondence to: Giuseppe DiBenedetto, Department of Cyto-pathology, Clinical Hospital, ViaSantella, 81025 Marcianise, Italy.Tel/fax +39-0823-690633;mobile +39-338-7184089;e-mail diben.g@libero.itReceived February 12, 2010;accepted May 18, 2010.Metastatic melanoma: an unusual presentationFerdinando De Vita1, Guido Giordano1, Alessio Fabozzi1, Barbara Guerrera2,Teresa Fabozzi1, Morena Fasano3, Marianna Ferrara2, Antonio Fascione4,and Giuseppe Di Benedetto51Division of Medical Oncology, F. Magrassi-A. Lanzara Department of Clinical and ExperimentalMedicine, Second University of Naples School of Medicine, II Policlinico, Naples; 2Division ofMedicine, Second University of Naples School of Medicine, Clinical Hospital, Marcianise; 3Divisionof Medical Oncology, F. Magrassi-A. Lanzara Department of Clinical and Experimental Medicine,Second University of Naples School of Medicine, II Policlinico, Naples; 4Department of ClinicalPathology, Clinical Hospital, Marcianise; 5Department of Cytopathology, Clinical Hospital,Marcianise, ItalyABSTRACTIn this report we describe a case of a malignant cutaneous melanoma metastasizingto the pleural surface and peritoneal cavity 5 years after surgical resection of the pri-mary lesion. Malignant cutaneous melanoma is a very aggressive cancer able tometastasize anywhere in the body. Pleural secondary lesions represent a rare eventdescribed only in a small number of patients and the association with peritoneal lo-calizations may suggest an uncommon pattern of spread that we discuss. Free full textavailable at www.tumorionline.itIntroductionCutaneous malignant melanoma is an aggressive cancer able to quickly and widelymetastasize. Its natural history is characterized by rapid spread to several sitesthrough different mechanisms including proliferation, neovascularization, em-bolism, local and lymphatic invasion. Systemic spread can be direct, lymphatic orhematogenous1,2.Metastases of melanoma may occur as satellite, regional lymph node or distantmetastases and may locate anywhere in the body, although the most common sitesare skin and lymph nodes (42-59%), lungs (18-36%), liver (14-20%), brain (12-20%),and skeletal bones (11-17%) 3,4. Intrathoracic localizations have been described in theliterature in several cases over the last 30 years, especially in the lungs. The pleuralsurface on the other hand is a very uncommon metastatic site. Pleural metastasis hasbeen described in only a few patients, rarely appears alone, and in 70% of cases is as-sociated with lung disease3,5. Lung, breast, stomach and ovarian cancer are the mostcommon primary tumors metastasizing to the pleura6.In this article we report a rare case of malignant cutaneous melanoma metastasiz-ing to the pleural surface and peritoneum after 5 years of progression-free survival.Furthermore, we describe the potential pathways of melanoma spread, focusing onthe relationship between pathological pleural effusion and peritoneal carcinosis.Case reportA 70-year-old woman with a history of HCV-related liver cirrhosis and stage IV ma-lignant melanoma of the right forearm (stage M1a with involvement of extraregional[axillary] lymph nodes), treated by surgical resection and lymphadenectomy in 2004,was admitted to our medical division with bilateral pleural effusion in September2009. During the last 4-5 months she had intermittent low fever, lasting 1-4 days, witha median temperature of 37.5 °C, peaks of 38.5-39 °C, and periods of apyrexia of 3-15Tumori, 97: 130-132, 2011METASTATIC MELANOMA 131days. In August of the same year she had undergone acontrast CT scan of the chest showing bilateral pleuraleffusion, more abundant on the right side, combinedwith lower lobe atelectasis and some enlarged mediasti-nal lymph nodes.On clinical examination decreased fremitus at thebase of the lung, especially on the right side, vesicularbreath sounds, and hypophonesis were noted, withoverall reduced lung expansiveness.This clinical presentation could be related to cirrhosisof the liver, in which pleural effusion is often described,but the previous history of malignant melanoma, even ifsurgically resected 5 years before, warranted a morespecific approach. In fact, considering that the patientwas already metastatic at the time of diagnosis ofmelanoma because of the involvement of axillary lymphnodes, the pleural effusion could be the expression of anew, even if uncommon, site of metastasis.For this reason the patient was submitted to a thora-cocentesis 8 days after admission, with cytological ex-amination of the pleural effusion. 250 mL of effusionfluid was extracted. Macroscopically, the fluid was tur-bid and pale yellow. Cytological examination revealed,in a background of mesothelial cells with atypical acti-vation, diffuse cellular elements with macronucleoli.The malignant melanoma cells were round or oval-shaped and showed extreme variability in size, rangingfrom 1 to 5 times the size of the background mesothelialcells. The presence of cytoplasmic melanin pigment wasvariable. All these features pointed to a diagnosis of asecondary melanoma lesion. We considered a pleuralbiopsy unnecessary because the cytology of the pleuralexudate was diagnostic.Oncological consultation based on these data sug-gested to complete tumor staging with CT of the brain,chest and abdomen with and without contrast, and to-tal-body bone scintigraphy7.The staging CT scan showed a few small solid oval-shaped lesions on the right pleural surface consistentwith melanoma metastasis (Figure 1A). We also ob-served extensive peritoneal thickening in associationwith bowel hyperdistension and crowding, a sign ofperitoneal carcinosis (Figure 1B). In view of themetastatic spread and the patient’s moderate clinicalcondition, palliative chemotherapy was proposed.Before starting treatment, the patient’s metabolic bal-ance worsened and she had severe respiratory and renalfailure, which caused her death.DiscussionPleural melanoma metastases are rare occurrences andin a high percentage of cases (>70%) are associated withmetastatic lung disease. Furthermore, the few cases re-ported were characterized by multiple lung nodules in 40-50% of patients and solitary nodules in only 20-30%8-10.The literature on this topic is scarce: in 1986 Wiebe etal. reported on the cases of metastatic malignantmelanoma occurring from 1970 to 1984 in their hospi-tal, describing only 2 patients with pleural metastasis11.The singularity of our experience is represented by theuncommon location of the secondary lesions and theunusual way of tumor spread. Primary melanoma com-monly metastasizes to the regional lymph nodes. In par-ticular, tumors located in the extremities and trunk witha thickness of more than 1.5 mm often have the tenden-cy to develop satellite or in-transit metastases.Neoplastic cells may follow an interstitial pressuregradient or secrete cytokines inducing growth of lym-phatic vessels towards or within the tumor12. Cells in-vading the extracellular matrix reach these lymphaticsand flow within them until the subcapsular sinus of thelymph nodes. Furthermore, it is known that melanomacells may secrete VEGF-C, an important lymphangio-genic factor in the tumor12.Based on our patient’s clinical history and the dataobtained by the staging exams, we hypothesized differ-ent pathways of spread. Impaired lymphatic drainagedue to the infiltrated mediastinal lymph nodes is theprimary mechanism for accumulation of pleural flu-id13,14. The pleural site may have been reached by malig-nant cells through the lymphatics; in fact, the disrup-tion of the normal architecture of the axillary space up-on surgical resection of the metastatic lymph nodescould have created lymphatic stasis, laying the basis forlate involvement of the pleural space by residual mi-crometastases.On the other hand, the lymphatic obstruction causedby the metastases on the diaphragmatic right pleuralsurface and anomalies of the diaphragmatic domecould have led to lymphatic backflow from the pleuralto the peritoneal space, which would explain the peri-toneal carcinosis (Figure 2).The time elapsed between the surgical resection andthe onset of metastasis can be explained by the conceptof tumor dormancy, according to which metastases of-ten occur many years after the diagnosis and treatmentFigure 1 - Chest and abdominal computed tomography showing bi-lateral pleural effusion more abundant on the right side where somesolid oval-shaped lesions can be seen on the parietal pleural surface(A). Conspicuous abdominal ascites with extensive peritoneal thick-ening combined with a few stretched and piled intestinal loops. Thispicture is strongly suggestive of peritoneal carcinosis.A B132 F DE VITA, G GIORDANO, A FABOZZI ET ALof a primary tumor. It has been suggested that themechanism underlying this phenomenon is the pro-longed persistence of tumor cells in a dormant state,probably due to the absence of adequate growth signal-ing or inhibition by tissue factors, or controlled by thehost immune response. As a consequence, there is alack of neoplastic proliferation, which may result in re-sistance to most of the chemotherapeutic agents avail-able today1.Carcinoma involving the pleura signals incurabilityand the only available therapeutic approach is palliativechemotherapy15. Different agents such as dacarbazine,fotemustine and temozolomide have shown activitywhen used alone and are endowed with a good safetyprofile16-18. In particular, a monochemotherapy regimenwith dacarbazine is considered the gold standard forfirst-line therapy, while fotemustine and temozolomidecan be considered valid alternatives15,18.In conclusion, this clinical presentation of metastaticmelanoma, even if unusual, should be taken into ac-count to obtain a complete diagnosis, so that the opti-mal therapeutic strategy to prolong the survival ex-pectancy can be planned.References1. Lopez M, Giacomini P, Carpano S: Melanoma. Oncologiamedica pratica, pp 1565-1596. Società Editrice Universo,Roma, 2005.2. Crowson AN, Magro CM, Mihm MC: The melanocytic pro-liferations. Wiley Liss, New York, 2001.3. Luckraz H, Morgan M, Gibbs AR, Butchart EG: Pseudome-sothelioma resulting from metastatic malignant melano-ma. Eur J Cardiothorac Surg, 28: 655-656, 2005.4. Loewenthal B, Shiau MC, Garcia R: Metastatic melanoma:an unusual diagnosis for a large anterior mediastinal mass.Radiographics, 24: 1714-1718, 2004.5. Kobayashi A, Bando M, Yoshiki I, Sugiyama Y, Kitamura S: Acase of pleural metastasis of malignant melanoma, dia-gnosed by thoracoscopy with regional anesthesia. Journalof the Japan Society for Bronchology, 21: 308-311, 1999.6. Chernow B, Sahn SA: Carcinomatous involvement of thepleura: an analysis of 96 patients. Am J Med, 63: 695-702,1977.7. Kuvshinoff BW, Kurtz C, Coit DG: Computed tomographyin evaluation of patients with stage III melanoma. AnnSurg Oncol, 4: 252-258, 1997.8. Kiser AC, Egan TM: Metastatic melanoma to the pleuralspace. Ann Thorac Surg, 74: 1257, 2002.9. Chen JT, Dahmash NS, Ravin CE, Heaston DK, Putman CE,Seigler HF, Reed JC: Metastatic melanoma to the thorax: re-port of 130 patients. AJR Am J Roentgenol, 137: 293-298,1981.10. Webb WR, Gamsu G: Thoracic metastasis in malignant me-lanoma: a radiographic survey of 65 patients. Chest, 71:176-180, 1977.11. Wiebe T, Wetzer K: Pulmonary and pleural metastases inmalignant melanoma. Z.Erkr Atmungsorgane, 167: 145-151, 1986.12. Zbytek B, Carlson JA, Granese J, Ross J, Mihm MC Jr, Slo-minski A. Current concepts of metastasis in melanoma. Ex-pert Rev Dermatol, 3: 569-585, 2008.13. Sahn SA: The differential diagnosis of pleural effusions.West J Med, 137: 99-108, 198214. Meyer PC: Metastatic carcinoma of the pleura. Thorax, 21:437-443, 1966.15. Garbe C, Peris K, Hauschild A, Saiag P, Middleton M, SpatzA, Grob JJ, Malvehy J, Newton-Bishop J, Stratigos A, Pe-hamberger H, Eggermont A: Diagnosis and treatment ofmelanoma: European consensus-based interdisciplinaryguideline. Eur J Cancer, 46: 270-283, 2010.16. Bajetta E, Del Vecchio M, Bernard-Marty C: Metastatic me-lanoma: chemotherapy. Semin Oncol, 29: 427-445, 2002.17. Middleton MR, Grob JJ, Aaronson N: Randomized phase IIIstudy of temozolomide versus dacarbazine in the treat-ment of patients with advanced metastatic malignant me-lanoma. J Clin Oncol, 18: 158-166, 2000.18. Avril MF, Aamdal S, Grobb JJ: Fotemustine compared withdacarbazine in patients with disseminated malignant me-lanoma. J Clin Oncol, 22: 1118-1125, 2004.Figure 2 - Abdominal computed tomography showing a potentialcommunication pathway between the pleural and peritoneal spacethat could explain the development of peritoneal carcinosis.View publication stats

Metastatic melanoma: An unusual presentation

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Metastatic melanoma: An unusual presentation

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