Primary Malignant Melanoma of the Esophagus

Chalkiadakis, George; Wihlm, Jean‐Marie; Morand, G; Weill-Bousson, M; Witz, J

doi:10.1016/s0003-4975(10)61963-7

Cited by 144 publications

(108 citation statements)

References 9 publications

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“…In humans, primary melanomas occur in the skin and other melanocyte-containing sites (eyes, meninges, anus, and vulva), or in sites where primordial melanocytes migrate (2,(21)(22)(23)(24)(25)(26)(27)(28). It was therefore conceivable that multiple lesions within the same RET.AAD mouse correspond to independent transformation events.…”

Section: Discussionmentioning

confidence: 99%

Tumor cells disseminate early, but immunosurveillance limits metastatic outgrowth, in a mouse model of melanoma

Eyles¹,

Puaux²,

Wang³

et al. 2010

J. Clin. Invest.

443

385

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Although metastasis is the leading cause of cancer-related death, it is not clear why some patients with localized cancer develop metastatic disease after complete resection of their primary tumor. Such relapses have been attributed to tumor cells that disseminate early and remain dormant for prolonged periods of time; however, little is known about the control of these disseminated tumor cells. Here, we have used a spontaneous mouse model of melanoma to investigate tumor cell dissemination and immune control of metastatic outgrowth. Tumor cells were found to disseminate throughout the body early in development of the primary tumor, even before it became clinically detectable. The disseminated tumor cells remained dormant for varying periods of time depending on the tissue, resulting in staggered metastatic outgrowth. Dormancy in the lung was associated with reduced proliferation of the disseminated tumor cells relative to the primary tumor. This was mediated, at least in part, by cytostatic CD8 + T cells, since depletion of these cells resulted in faster outgrowth of visceral metastases. Our findings predict that immune responses favoring dormancy of disseminated tumor cells, which we propose to be the seed of subsequent macroscopic metastases, are essential for prolonging the survival of early stage cancer patients and suggest that therapeutic strategies designed to reinforce such immune responses may produce marked benefits in these patients. IntroductionMetastatic disease is the major cause of death by cancer (1, 2). Metastasis is a complex multistage process that requires cancer cells within the primary tumor to invade the local tissue and enter the blood or lymphatic vessels. Tumor cells need to survive in the circulation and migrate across vessel walls in order to colonize new sites and grow to form secondary tumors (3). The traditional view has been that tumor cell dissemination occurs late in cancer development (4-6); however, this notion has recently been challenged. Several expression profiling studies (7-10) suggest that the propensity of cancer cells to metastasize is acquired relatively early during tumor progression (reviewed in ref. 11). In addition, examination of bone marrow from early stage cancer patients without overt metastases (reviewed in refs. 12 and 13) and tumorbearing mice (14) revealed that disseminated tumor cells (DTCs) are present at much earlier time points than expected. We now need to understand the significance of these DTCs. Specifically, we must determine how early DTCs contribute to clinically relevant macrometastases and identify the mechanisms involved in the development, maintenance, and breakdown of dormancy.Transplanted tumor models in rodents are often used to study metastasis, with most of our current knowledge of cancer cell dissemination being drawn from xenograft models. However, these models often fail to recapitulate the gradual process of tumorigenesis that is observed in humans, and, in the case of immuno-

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Section: Discussionmentioning

confidence: 99%

Tumor cells disseminate early, but immunosurveillance limits metastatic outgrowth, in a mouse model of melanoma

Eyles¹,

Puaux²,

Wang³

et al. 2010

J. Clin. Invest.

443

385

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“…Primary malignant melanoma of the esophagus (PMME) is a rare malignant disease, accounting for only 0.1-0.2% of all esophageal neoplasms. The mean survival time from diagnosis is only 13.4 months, and the five-year survival rate is 4.2% worldwide (3,4).Definitive diagnoses may be confirmed by pathological analysis and positivity for S-100, human melanoma black (HMB)-45 and melanoma-specific antigen (Melan-A) proteins on immunohistochemical examination. Surgical extirpation is the standard treatment for PMME.…”

Section: Introductionmentioning

confidence: 99%

Primary malignant melanoma of the esophagus: A case report and review of the literature

2015

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Abstract. Primary malignant melanoma of the esophagus (PMME) is a rare malignancy and the prognosis is typically poor. There is currently a lack of appropriate treatment strategies and clear guidance. The current study presents the case of a 65-year-old female with a two-month history of progressive dysphagia, the investigations of which resulted in a diagnosis of PMME. The patient was treated with a radical transhiatal esophagectomy with subcarinal lymphadenectomy followed by combined chemoimmunotherapy. The patient remains alive with no evidence of tumor progression at the 12-month follow-up. The purpose of the present study was to report a new case and to review the recent relevant literature regarding the treatment of PMME.

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“…There is no known genetic disposition, nor are alcohol consumption, smoking or gastric regurgitation proven risk factors. PMME may be found in all areas of the esophagus, but has been located in the lower twothirds of the esophagus in 86% of the cases [7]. The characteristic finding at endoscopy is a polypoid irregularly pigmented lesion.…”

Section: Introductionmentioning

confidence: 99%

Asymptomatic Primary Malignant Melanoma of the Esophagus

Gerger

Smolle‐Jüttner²,

Samonigg³

et al. 2007

Oncol Res Treat

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Primary malignant melanoma of the esophagus is an exceedingly rare disease. This tumor is typically aggressive and disseminates early via the lymphatics and the bloodstream with a mean survival time between 10 and 15 months after radical surgical resection. The role of chemotherapy and immunotherapy is unclear. No treatment plan for the disease has yet been established. Case Report: A 78-year-old man came for a checkup with a medical history of reflux esophagitis and chronic gastritis. Esophagogastroscopy showed a bluishgray tumor of the esophagus, and histology revealed features consistent with malignant melanoma. The patient underwent total transhiatal esophagectomy with curative intention, and esophagogastric anastomosis was performed. Immunohistochemistry revealed tumor cells strongly positive for the melanoma-specific antigen HMB45 and protein S-100, and negative for cytokeratin. A proposed postoperative chemotherapy was declined by the patient. Nine months after surgery, the patient’s condition deteriorated, and a mediastinal lymph node conglomerate was found. Two months later, he died of bleeding into the cervical soft tissue. Conclusion: Up to date, radical surgical resection is the main treatment. Very little is known about the benefits of chemotherapy and immunotherapy. However, these therapeutic modalities may play an important role in the future.

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Primary Malignant Melanoma of the Esophagus

Cited by 144 publications

References 9 publications

Tumor cells disseminate early, but immunosurveillance limits metastatic outgrowth, in a mouse model of melanoma

Tumor cells disseminate early, but immunosurveillance limits metastatic outgrowth, in a mouse model of melanoma

Primary malignant melanoma of the esophagus: A case report and review of the literature

Asymptomatic Primary Malignant Melanoma of the Esophagus

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