Skip Navigation LinksHome > May 2011 - Volume 18 - Issue 3 > Primary Malignant Melanoma of the Esophagus: A Clinicopathol...
Advances in Anatomic Pathology:
doi: 10.1097/PAP.0b013e318216b99b
AMR Series

Primary Malignant Melanoma of the Esophagus: A Clinicopathologic Study of a Case With Comprehensive Literature Review

Bisceglia, Michele MD*; Perri, Francesco MD; Tucci, Antonio MD; Tardio, Matteo MD§; Panniello, Gaetano MD; Vita, Giulia MD‡‡; Pasquinelli, Gianandrea MD

Free Access
Article Outline
Collapse Box

Author Information

Departments of *Pathology, Division of Anatomic Pathology

Medical Sciences, Division of Gastroenterology

§Surgical Sciences, Division of Abdominal Surgery, IRCCS “Casa Sollievo della Sofferenza” Hospital, San Giovanni Rotondo

Etromapmax Pole, Biomedical Sciences School, Lesina (FG)

Department of Specialistic Medicine, Clinical Dermatology, Ospedali Riuniti di Foggia, Foggia

‡‡Unit of Anatomic Pathology, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture (PZ), Italy

Department of Hematology, Oncology, and Clinical Pathology, Division of Surgical Pathology, Policlinico “S. Orsola” and University of Bologna, Bologna, Italy

Reprints: Michele Bisceglia, MD, Department of Pathology, Division of Anatomic Pathology, IRCSS “Casa Sollievo della Sofferenza” Hospital, V.le Cappuccini, 71013 San Giovanni Rotondo), Italy (e-mail: bismi@libero.it).

All figures can be viewed online in color at http://www.anatomicpathology.com

Collapse Box

Abstract

Primary malignant melanoma originating in the digestive tract is particularly rare, mainly affecting the anorectum and oral cavity. Primary malignant melanoma of the esophagus has been the subject mostly of case reports. This tumor has a dismal prognosis with a frequency estimated to be approximately 0.1% to 0.2% of all esophageal malignancies. According to the review by Volpin et al of November 2002, 238 cases of primary malignant melanoma of the esophagus have been published up to early 2001. We present an additional case of primary malignant melanoma of the esophagus of the amelanotic variant in a 69-year-old man. The patient was preoperatively investigated by esophageal endoscopy and endoscopic ultrasound. The surgically resected tumor specimen was examined histologically and supplemented by immunohistochemical and ultrastructural analysis. Intra-abdominal relapse occurred after 8 months at the site of surgery, necessitating repeat resection. The patient died of advanced intra-abdominal disease 14 months after the primary diagnosis. A comprehensive computerized (PubMed/Medline) review of the world literature was also carried out and 99 additional cases (after the review by Volpin et al) were found, 9 of them from the 1990s which escaped previous tabulations, and 90 from the years 2000 to 2010, amounting to a grand total of 337 ever published.

Back to Top | Article Outline

OVERVIEW

Diagnosis: Primary malignant melanoma of the esophagus.

Referral sources: The first International AMR Symposium in Anatomic Pathology, 19 to 21 June, 2002, San Giovanni Rotondo, Italy—case no. 36 (slides labelled 32074-1), contributed by M. Bisceglia, MD, San Giovanni Rotondo, Italy, and presented by Saul Suster, MD, formerly at The Ohio State University, Columbus, OH.

Back to Top | Article Outline

CLINICAL HISTORY

In August 2001 a 69-year-old man was admitted to the “Casa Sollievo della Sofferenza” hospital (San Giovanni Rotondo, Italy) for complaints of abdominal distress and melena. This patient had never undergone surgery nor diagnosed previously with malignancy. On endoscopic examination, a polypoid tumor was discovered in the lower third of the esophagus, at 37 cm from dental ridge (incisors), also involving the cardia (Fig. 1). Endoscopic ultrasound (EUS) to assess tumor depth and lymph node status was also performed and confirmed an area of mural thickening of the distal esophagus, with tumor infiltration limited to the submucosal layer, in the absence of periesophageal and mediastinal lymph node involvement (uT1uN0) (Fig. 2). The polypoid lesion was actively bleeding at the time of examination and successful endoscopic hemostasis was achieved by submucosal injection of adrenalin. An endoscopic biopsy showed a poor1y differentiated, malignant neoplasm, consistent with several possibilities, including that of undifferentiated, amelanotic melanoma. The patient underwent partial esophagectomy with total gastrectomy, and a Roux-en-Y esophagojejunostomy was performed for reconstruction (Fig. 3).

Figure 1
Figure 1
Image Tools
Figure 2
Figure 2
Image Tools
Figure 3
Figure 3
Image Tools
Figure 4
Figure 4
Image Tools

The surgical specimen was sent for pathologic examination. The resection specimen showed a large, ulcerated, partly fungating, tan red mural mass of 6 cm in greatest diameter. Histologic examination showed a malignant neoplasm composed of solid sheets or discrete nests of monotonous, highly malignant, epithelioid tumor cells with large nuclei and prominent nucleoli. Areas of hemorrhage and necrosis were evident throughout all sections. Mitotic figures were numerous (>50 per 10 HPF) (Fig. 4A–D). The tumor was deeply infiltrating into the muscularis propria, with some figures of lymphatic vessel invasion. On the surface, at the margin of the ulceration near the gastroesophageal junction, focal junctional melanocytic activity was found in the basal layer of the squamous epithelium (Fig. 4E–H). Clear-cut pagetoid spread was not seen due to the extensive tumor ulceration and melanosis was not documented in the healthy adjacent mucosa. Histochemical stains for mucin (PAS-D and mucicarmine) and for argentaffin granules of melanin (Fontana) were negative in the tumor cells. Immunohistochemically the tumor was strongly positive for vimentin, S-100 protein, HMB45, and Melan-A, and negative for cytokeratin AEl/AE3, carcinoembryonic antigen, MOC31, actin, desmin, epithelial membrane antigen, CD10, CD20, CD45, CD99, CD117, and alpha-fetoprotein, thus attesting to the melanocytic nature of the tumor (Fig. 5A–E). Incidentally for the purpose of this report we also recently tested the tumor for MiTF, which was largely positive in tumor cell nuclei (Fig. 5F). In confirmation, electron microscopic examination was also carried out at the time of the original diagnosis on small pieces of tissue retrieved from the paraffin block, which showed stage I premelanosomes and stage II melanosomes in some of the cells (Fig. 6A–D). A total of 15 perigastric and periesophageal lymph nodes examined were all free of tumor.

Figure 5
Figure 5
Image Tools
Figure 6
Figure 6
Image Tools
Back to Top | Article Outline
Diagnosis

The final established diagnosis was that of primary amelanotic malignant melanoma of the esophagus. (stage: pT2, pN0, pMx).

Back to Top | Article Outline
Follow-up

Careful physical examination of our patient after the postoperative diagnosis did not show any cutaneous, mucosal, or ocular lesions suspicious for melanoma or any other tumor elsewhere in the body. The patient was then given adjuvant immunomodulatory therapy with subcutaneous injection of interferon-α (Roferon-A 3 MV) on alternate days which was planned for 48 weeks. Eight months after surgery the patient complained of a new episode of melena due to a regional melanoma relapse histologically documented on endoscopic biopsy, involving the jejunojejunal anastomosis (Fig. 7), located at 65 cm from the dental ridge. A new surgical bowel resection including the jejunojejunal anastomosis was performed. Reconstruction was then accomplished with a proximal jejunojeunal terminoterminal anastomosis between the 2 ends of the efferent loop and a distal jejunojejunal terminolateral anastomosis between the afferent and the efferent loops. The surgical specimen was histologically examined and the melanoma recurrence confirmed. Immunotherapy was subsequently continued, but the patient eventually died of advanced stage intrabdominal disease 14 months after the primary diagnosis.

Figure 7
Figure 7
Image Tools
Back to Top | Article Outline

AUTHORS' COMMENTS

Primary malignant melanoma originating in the internal organs is rare, but well documented in the literature.1 Primary malignant melanoma originating in the digestive tract is particularly rare, affecting in decreasing order of frequency the anorectum, oral cavity, esophagus, stomach, small bowel, gallbladder, and large bowel.1–3 Primary malignant melanoma of the esophagus has been the subject mainly of case reports, and its frequency is estimated to be approximately 0.1% to 0.2% of all esophageal malignancies.4 In the United States, based on the SEER* Stat Software database (National Cancer Institute, Bethesda, MD), 39 cases of primary malignant melanomas of the esophagus (5.9%) were found from 1973 to 2004 of a total of 659 primary melanomas of the gastrointestinal tract,3 and in a large epidemiologic study the age-adjusted rate incidence (median age, 69 y) was 0.03 per million population a year.5 In November 2002 Volpin et al,6 updated the review of the world literature on this subject, starting from the previous works of Sabanathan et al,4 Taniyama et al,7 and Joob et al,8 and established the total number of cases reported up to early 2001 at 238, beginning in 1906 when a case of melanoma in the esophagus was first observed by Baur.9 There are an additional 9 cases by several investigators, dating back to the 1990s, which escaped previous calculations and are also to be included, that is, 1 case each reported by Loftus et al,10 Al-Karawi et al,11 Deligeorgi-Politi and Kairi-Vassilatou,12 Chan and Nambiar,13 Kinuya et al,14 Simonov et al,15 and 3 cases by Lam et al.16

On the basis of a computerized (PuMed/Medline) bibliography search, from January 2000 to the end of October 2010, we retrieved a total of 96 cases of primary malignant melanoma of the esophagus from which, after subtracting 6,17–22 from the overlapping 2000 to 2001 period, which were already included in the review of Volpin et al,6 90 were considered genuinely new (Table 1).23–89 Adding these 2 sets of 9 and 90 cases, from the last decade of the past century and from the first decade of this current one, respectively, the grand total amounts to 337 cases ever published. However, we did not list in our tabulation those cases of primary malignant melanoma of the esophagus, reported in studies not cited in PubMed/Medline, which we incidentally came across in reviewing various reference lists,90–94 and cases which were not fully reported but included in epidemiologic and survival rates studies from Cancer Registries, covering interval decades and/or related to melanomas of gastrointestinal tract in general.1,3,5,95 Somewhat arbitrarily we also left out of the list a case of melanoma in situ associated with multifocal squamous cell carcinoma in situ, which was defined by the reporting investigators as “atypical melanocytic proliferation,” and which disappeared on follow-up and was thought to be of a reactive nature due to coexisting reflux esophagitis.96

Table 1
Table 1
Image Tools

Primary malignant melanoma of the esophagus is thought to originate from foci of basal melanocytes, which are normally present in the basal layer of the esophageal squamous epithelium in 4% of individuals.97–99 Primary malignant melanoma of the esophagus occurs mostly (>90%) in the mid and lower third of esophagus,4,74Table 1 the anatomic sites where these melanocytes are more concentrated. Neither sun exposure, specific alimentary diet, nor personal habits, such as alcohol and smoking, have been suspected to be predisposing factors in the pathogenesis of this tumor.5 Racial differences have been documented and primary malignant melanoma of the esophagus, contrary to skin melanoma, is more common in Japanese than in whites.1,6,8 and refs. in Table 1.

The clinical features of primary malignant melanoma of the esophagus are similar to those of carcinoma of the esophagus. Most patients are in their sixth and seventh decades,4 with only 1 pediatric case recorded.100 Male individuals predominated, with a 2.02:1 male-to-female ratio, in the review of Sabanathan et al,4 and slight male individual predilection has been also noted in our review [sex ratio of 55 to 32 of 87 patients for whom sex was stated or available (Table 1)]. No familial case or individual genetic predisposition for primary malignant melanoma of the esophagus has been observed. Dysphagia, substernal pain, heartburn, and weight loss are the most common symptoms, usually dating back few to several months before diagnosis. Melena, due to bleeding from the tumor is another complaint sometimed reported (7% in the review of Sabanathan et al),4 and there are also 2 cases presenting with hypovolemic shock due to severe bleeding, one with massive melena and the other with hematemesis.31,101 Grossly the tumors are most often polypoid and ulcerated, and can vary in size from small lesions to large, bulky sessile masses, whereas only a minority present as plaque-like tumors or as diffuse thickened, almost concentric, stricture-like lesions (Table 1). Occasionally, polypoid tumors are pedunculated,26,27,46 with a stalk of variable thickness. Very few cases present as flat-type, usually with early-stage invasion.47,48,50,80,94 The majority of the tumors are grossly pigmented; however, totally amelanotic lesions can occur, amounting to 10% to 25% of all primary malignant melanomas of the esophagus.7,8 Of the 90 cases listed in Table 1, including our case, 16 in overall were grossly amelanotic with histologic confirmation,29,40,44,46,50,51,53,57,72,78,90 but in a single series of 10 cases of Lohmann et al40 5 were amelanotic. Primary malignant melanoma of the esophagus may also appear as multiple nodules, varying from closely packed (multilobulated tumor) to well-separated nodules even at an appreciable distance. In the latter circumstance, one can see a main mass with single-to-multiple small satellite nodules,4,6,29,44,54,62,75 in Table 1 which are usually interpreted as submucosal intramural metastases but also as independent tumors. In our review we found satellite nodules in 5 cases29,44,54,62,75 in Table 1. However, in one case 2 grossly similar synchronous tumors were found68 and in another case 2 metachronous melanomas occurred.47 Primary malignant melanoma of the esophagus may be observed also in association with other local or systemic, inflammatory or neoplastic diseases: in 2 cases primary malignant melanoma of the esophagus arose on a background of Barretts' esophagus30,59 and was combined (as a collision tumor) with adenocarcinoma in 1,59 in another case there was a long-standing clinical history of serum HIV positivity75 and occasionally an unrelated former or synchronous or second cancer has been found in the patients' medical history or during workup or follow-up of their primary malignant melanoma of the esophagus.51,57,64,67,102 Lastly, a unique case of synchronous quadruple cancer has been also recorded.103

Histologically, primary malignant melanoma of the esophagus usually appears as a large epithelioid, spindle, or small cell malignant neoplasm, characterized by the presence of cytoplasmic melanin granules, already visible on routinely hematoxylin and eosin-stained sections or shown by special stains. Less frequently this tumor may appear completely amelanotic, even after histochemical stains for melanin (eg, Fontana stain) have been applied, as in our case. The microscopic features of locally advanced tumors are usually those of a high-grade malignancy, with necrosis, numerous mitoses, frequent ulceration, and lymphatic vessel invasion. Primary malignant melanoma of the esophagus has a tendency for vertical growth within the esophageal wall. However, thanks to esophagoscopy and to some health surveillance screening programs, nowadays some of the tumors are discovered in the early stages of invasion, limited to the mucosal or submucosal layers, or even in their in situ phase of growth.17,21,48,71,94 The histologic report, especially for cases of early-stage invasive tumors, should include measurements of tumor thickness, as this parameter may have prognostic significance,40 though no systematic study has been done as of yet in this regard.

The differential diagnosis for primary malignant melanoma of the esophagus, particularly the amelanotic variant, is quite broad: poorly differentiated carcinoma, gastrointestinal stromal tumor, other malignant mesenchymal neoplasms, such as leiomyosarcoma and malignant peripheral nerve sheath tumor, including melanocytic schwannoma,104 and non-Hodgkin malignant lymphoma are usually considered. Immunohistochemistry should be able to clearly define the melanocytic nature of the tumor cells, based on the expression by tumor cells of classic immunomarkers, such as vimentin, S-100 protein, HMB-45, Melan-A, and tyrosinase, usually in the absence of expression of epithelial, smooth muscle, and lymphoid markers. To the best of our knowledge immunoreactivity for MiTF, which was documented in our case, had not been previously investigated in this tumor. Analogous to its cutaneous counterpart, primary malignant melanoma of the esophagus might be expected to express female steroid hormone (progesterone and estrogen) receptors, and this is the biological basis for the favorable response to adjuvant hormone therapy (tamoxifen) seen in some cases44,50,55; however, hormone receptor expression was not documented in the first (likely the only) immunohistochemical study specifically carried out in 3 cases.16 Again, similar to skin melanomas,105 primary malignant melanoma of the esophagus can also show immunoreactivity for KIT and PDGFRA proteins,72,78,88 but in the absence of KIT and PDGFRA gene mutations,78 which explains the lack of response of melanomas to imatinib therapy. Immunoreactivity of primary malignant melanoma of the esophagus for KIT and PDGFRA should be kept in mind due to the possibility of confusing this tumor with gastrointestinal stromal tumor, especially when dealing with small endoscopic biopsies, though we acknowledge the rarity of the latter in the esophagus. More frequently, dealing with small endoscopic biopsies, primary malignant melanoma of the esophagus is preoperatively misdiagnosed as poorly differentiated and nonkeratinizing squamous cell carcinoma.4,6,30,51,55,57,74 Ultrastructurally, it is similar to melanomas of other sites, showing melanosomes and premelanosomes, as we could document in the case herein presented, and as was also shown in 3 other previously cases so studied.16,106,107 For electron microscopic examination we did not use fresh tissue, but successfully retrieved small pieces of tumor tissue from the paraffin block, and this technique and modality may occasionally be helpful particularly in difficult cases.

However, the main differential diagnosis of the tumor in point is with a metastasis to this organ from primary melanoma of another site. There are both histologic and clinical parameters, which can help with this determination. The most important histologic feature suggestive of primary malignant melanoma of the esophagus is the identification of atypical junctional melanocytic activity in the basal layer of the squamous epithelium overlying the tumor6,74 [and refs therein] or the existence of an adjacent melanoma in situ (Table 1), one or the other having been found in 10 of 89 total cases reviewed (Table 1). Evidence of pagetoid spread is also in favor of primary versus metastatic involvement,6,74 even though large tumors are often ulcerated, and may no longer show viable overlying epithelium, and metastatic tumors when secondarily infiltrating the overlying mucosa can also give rise to a (picture closely resembling a) pagetoid pattern of growth. Melanosis is another important feature favoring primary malignant melanoma of the esophagus over a metastatic melanoma to the esophagus. “Melanosis” of the esophagus is the phenomenon of melanic pigmentation (melanoplakia) of various lengths of the mucosa at the edges of primary malignant melanoma of the esophagus, histologically corresponding to an increase of benign melanocytes and melanin granules in the basal layer of the epithelium.74,99,108–110 It usually forms single or multiple pigmented patches, restricted to the region adjacent to the main tumor, but it can also be diffuse71,111,112 and extend throughout the esophagus.4 Melanosis, according to some “melanocytosis,” is more common in Indians and Japanese than in Europeans and non-Hispanic American whites.99,109,113 Melanocytic proliferation in melanosis may be incited by chronic esophagitis due to gastroesophageal reflux disease.99,109,113 Usually, the melanocytic proliferation (melanocytosis) in melanotic patches does not exhibit any sign of nuclear or cellular atypia, even though atypical forms, approaching the histologic features of melanoma in situ have been described.96 The association of melanosis with primary malignant melanoma of the esophagus is seen in around one fourth to one third of the surgical resection specimens with primary melanomas,6,40 and, according to some, a melanotic area of esophageal mucosa should be considered a condition which may predispose to or transform into primary malignant melanoma of the esophagus.6,111,114 In our review of the literature of such tumor, melanosis was seen, both endoscopically and histologically, in approximately 20 cases of 90, but this is probably an underestimation (Table 1). In a few cases transformation of the melanotic lesion into (invasive) primary malignant melanoma of the esophagus was well documented either in following the lesion up with biopsies taken at time intervals37,66 as the appearance of black (melanomatous) patches in wider brownish-dark (melanotic) areas50 in form of a polypoid tumor adjacent to a melanotic patch histologically corresponding to atypical melanocytic hyperplasia,41 or as a flat lesion on the background of diffuse melanosis with melanocytic atypia and foci of melanoma in situ.115,116 Melanosis of the esophagus was even seen in association with melanoma of other sites (anal melanoma117) and may also be observed in association with squamous cell carcinoma,66,109 in Addison disease,109 and in Laugier-Hunziker syndrome,109 which is a condition of hyperpigmentation of oral mucosa associated with pigmentation of the nails due to increased melanocytes. Melanosis of esophagus may be mimicked by esophageal anthracosis,118 a rare condition, which may need careful histologic examination and on biopsy may be difficult to differentiate from melanoma itself.118

Notwithstanding the most reliable criterion to differentiate primary malignant melanoma of the esophagus from metastatic melanoma to esophagus is to rule out clinically and on thorough physical examination the existence of a primary melanoma in the most usual anatomic locations (skin, eye, anorectum, and oralnasopharynx). In addition, the virtual absence on clinical work-up of evidence of tumor in the parenchymal visceral organs at the time of the diagnosis of esophageal melanoma is a helpful clinical feature in favor of primary malignant melanoma of the esophagus, as metastatic melanoma is usually multiple and presents with lesions in other organs. The majority of metastatic melanomas to the esophagus occur in the context of advanced or very late stages of the disease3,74 and, though metastases of melanoma to gastrointestinal tract are common, involvement of the esophagus is rare, being found in only 4% of overall gastrointestinal metastases from cutaneous melanomas.119 Primary malignant melanoma of the esophagus is thus more frequent than metastasis in the esophagus, and a solitary metastasis to the esophagus from an occult primary, although possible, would be very unlikely, being recorded only in 11 cases so far.112 Occasionally, primary malignant melanoma of the esophagus itself may give rise to metastases to other parts of the gastrointestinal tract, mainly to the stomach, which may be discovered both at postmortem examination4 and more rarely during follow-up, in the form of intraluminal metastases.83

In our case the presence of focal adjacent junctional melanocytic activity and the absence of melanoma in any other cutaneous, mucosal (anorectum and oralnasopharynx), or ocular location on thorough clinical examination, both supported a diagnosis of primary malignant melanoma of the esophagus. In addition, from the follow-up, the absence of clinical development of other specific lesions after 8 months in other locations other than a regional recurrence at the site of surgery substantiates the above assertion. In fact, tumors that recur locally (or regionally) before they give rise to distant metastases are most likely primary lesions rather than repeat metastases to the same location from an occult primary (the “Toker” law). Noteworthy in our patient was the regional relapse at the level of the jejuno-jejunal anastomosis. Noteworthy in our patient was the regional relapse at the level of the jejunojejunal anastomosis. Local recurrence at the level of the esophagojejunal anastomosis would seem more logical, as primary malignant melanoma of the esophagus has a tendency to disseminate by the submucosal lymphatic route with possible formation of tiny satellite nodules, which may not have been noticed with the naked eye during operation. Local recurrences at the site of surgery are well documented both in primary malignant melanoma of the esophagus and in other esophageal malignancies and have always been described at the site of the esophageal anastomosis (ie, esophagogastric anastomosis, esophagojejunal anastomosis, esophagocolic anastomosis). This is the first report of local tumor recurrence skipping the first line of surgery to reach the second line (Fig. 7): we propose as a pathogenetic explanation for this puzzling event (which still remains difficult to explain) mechanical contamination by tumor (hypothetically carried by a surgical instrument) of the involved anastomosis during surgery. Secondary tumor implantation has been well documented in other organs and in various situations, such as that of uterine cervical involvement by endometrial carcinoma of the corpus after curettage120 and intradermal implantation of breast carcinoma in the track of a previous needle biopsy [personal unpublished observation of one of us (M.B.)]. Any other hypothesis, including lymphatic or hematogenous dissemination from the original primary malignant melanoma of the esophagus to a very special surgery site, metastatic seeding from a second virtual primary melanoma of unknown origin which after metastasizing to the esophagus in isolation the first time did so again to a well-defined surgical site the second time, or finally metastasis from a second (as well as occult) primary melanoma other than the primary malignant melanoma of the esophagus we diagnosed, would be much more illogical.

Primary malignant melanoma of the esophagus is quite aggressive, likely more so than its cutaneous counterparts, but this may be due in part to their larger size and depth of invasion at the time of diagnosis. More than 50% of patients are found to have metastatic disease at the time of presentation.4,6,121 In our review lymph node and/or distant metastases were found in 46 of a total of 90 cases (Table 1). Regional lymph node metastases are largely unrelated to the depth of invasion by the primary tumor6,121 and in our review we found 10 pN1 stages out of 28 pT1 total cases (Table 1). In addition to regional and nonregional lymph nodes (cervical and celiac axis nodes), common sites of metastases are the lung, liver, mediastinum, brain, and bone, but distant metastases may occur even in the gastrointestinal tract itself, adrenal, and kidney.4,6,120,121 Distant metastases may supervene after years also in cases with apparently early-stage primary malignant melanoma of the esophagus, with invasion limited to the submucosa, and this was observed in 8 of 18 T1N0 cases (17pT1pN0 and 1 cT1N0) we reviewed (Table 1).28,32,33,47,57,60,74,76,86,89 Even cases with invasion limited to the mucosa are at risk, as shown by one case in which distant metastasis (to the liver) was observed 7 years after diagnosis94 and by another in which lymphatic and blood vessels invasion were histologically documented.48 Metastasis can be well detected by means of 18F-Flourodeoxyglucose positron emission tomography as both primary and metastatic localizations are characterized by increased uptake of the radiotracer (Table 1).

Complete excision by surgical resection is the standard treatment and the only treatment modality that influences survival.3 Radical surgery, (partial to subtotal to total) esophagectomy and 3-field lymphadenectomy, including periesophageal, mediastinal, and celiac axis lymph node dissection, is the treatment of choice when feasible.3,6,121 For melanomas of the lower third of the esophagus, involving the cardia or primary tumors of the cardia, involving the gastric fundus, the surgical operation is total gastrectomy extending to the lower esophagus. Surgical resection margins need to be wider than is the case with other malignant neoplasms because—as previously discussed—of the not infrequent presence of satellite nodules. The overall mean survival time for primary malignant melanoma of the esophagus after operation is approximately 10 to 14 months, with a 5-year survival of approximately 4.5%,4,121–123 whereas at this time there is no 5-year survival with other modalities4 and Table 1 Volpin et al6 analyzed data from the literature from the 1990s and, although based on a small number of cases (25 cases examined), found a 5-year survival value of 37% in patients undergoing surgical resection. We did not perform statistics calculation on survival, as it was not a goal of this review, and therefore we refer the reader to the follow-up data in Table 1. However, without in depth statistical analyses, we note that of 77 cases for which follow-up was available, 20 patients were alive after 24 months or more (26%), 5 were alive after 36 months or more (mid-term survivors—6.5%), and 4 survived 60 to 184 months (long-term survivors—5.2%). All these patients underwent surgery with lymph node dissection except for 2 (1 who received endoscopic polypectomy and 1 who refused surgery and was treated with radiotherapy): in addition, 11 of these patients were given adjuvant therapy, including the case who was treated with polypectomy.

The effectiveness of adjuvant radiation therapy, chemotherapy, and immunotherapy is controversial. In some cases with inoperable obstructive large tumors, palliative restoration of luminal digestive continuity may be obtained with conventional radiation therapy, by using intraluminal brachytherapy, or by insertion of a metal stent (Table 1).25,37,42,43,45,84 In some cases lymph nodal metastatic masses have been locally irradiated with apparent complete or partial regression of tumor.26,45 Chemotherapy usually includes dacarbazine, nimustine, vincristine, and cisplatin. Paclitaxel (formerly called taxol, of the drug category of taxanes) was administered in one case55 as a fourth line of therapy with favorable partial response. Immunotherapy may be promising and is currently expanding from classical administration of interferon to new immunomodulators, based on active dendritic cells vaccination and passive immunotherapy with lymphokine-activated killer cells, and monoclonal-based targeted therapy directed to melanoma antigens present on tumor cells.40,49,60 Adjuvant endocrine therapy has been used in few cases of primary malignant melanoma of the esophagus44,50,55,124 in combination with chemotherapy. As the expression of survivin in tumor cell nuclei in this tumor has been documented, treatment with inhibitors of survivin aiming to increase the rate of apoptosis and the sensitivity of tumor cells to chemotherapeutic drugs and irradiation in primary malignant melanoma of the esophagus has been proposed. However, this treatment modality is still in a preclinical phase for primary malignant melanoma of the esophagus as for other cancers.

Local endoscopic laser ablation also may play a role in the palliation of locally advanced tumors that are unresectable.40,42 For pedunculated polypoid tumors, in some circumstances, and in the absence of suspected lymph node metastases, endoscopic resection (polypectomy) may be an option,27,62,92 possibly the preferred one in the presence of coexisting illnesses which discourage surgery, taking into consideration the 15% postoperative mortality rate of standard surgery with thoracotomy. Endoscopic mucosal resection (EMR) should be restricted to highly selected cases of early primary malignant melanoma of the esophagus and must be complemented by careful post-excision histologic examination ensuring tumor-free margins and subsequent close follow-up, and could be successfully applied even repeatedly to its flat-type (superficial) variant.48,94

EMR is assisted by preliminary EUS for the preoperative assessment of the depth of the tumor invasion and lymph node status, and is indicated for tumors limited to the mucosal layer and precluded for tumors invading the submucosal layer or in the presence of metastatic lymph nodes. EUS which is currently a means of routine investigation for intraluminal neoplasms of the digestive tract was first used in primary malignant melanoma of the esophagus in 1996.125 This tumor usually appears as a hypoechoic mass or has mixed echogenicity at EUS in comparison with the healthy tissue of various esophageal layers. Several cases of primary malignant melanoma of the esophagus have been investigated in this way,34,48,51,52,66,67,79 with postoperative pathologic assessments (pT, pN) usually in accordance with the predictions of EUS preoperative staging evaluations (uT, uN).

On the whole, most patients are still currently diagnosed at an advanced stage and only a few at an early stage. Improving the outcome of this aggressive malignancy with lowering of the overall mortality rate may be achieved mostly with early diagnosis. In our most recent review of the literature of the last decade, herein presented, based on the parameters given by the reporting investigators, we could evaluate pT staging in only 62 cases of 90, whereas most of the rest were inoperable having advanced-stage disease as attested by early death or early evidence of systemic metastases: of these 62 cases, 31 were T1 tumors, while 21 were T2 and 10 T3-T4 taken together (Table 1). Only 1 case was discovered in its in situ stage71 in Table 1 and 2 cases were intramucosal (invasion limited to the lamina propria)48,71 in Table 1. Parenthetically, with regard to T1 stage melanomas: no tumor limited to the epithelium was found in the extensive review of 139 cases by Sabanathan et al,4 published in 1989; only 1 case of melanoma in situ17 and 1 case of intramucosal melanoma, respectively, were included in the review of Volpin et al,6 published in 2002; and only 4 cases in total we found, while preparing this study, of which 3 (1 melanoma in situ and 2 intramucosal) were on record in PubMed/Medline and we already just quoted above48,71 in Table 1 and 1 more94 we encountered of our referential database, and therefore not listed in our tabulation.

Though T1-adjusted long-term survival rates are hindered by the short follow-up available for many of them at the time of publication; all patients who survived 36 months or more had T1 tumors (Table 1),50,60,64,71,74 except for a unique case, a pT2pN0 Chinese patient who died after 17 years due to lung cancer. Moreover of the 4 long-term survivors, living for >60 months in our review, 3 were pT1 (2 pT1pN0, 1 pT1pN1) and 1 was pT2 (pT2pN0) (Table 1)40,47,64,81: one of these was a patient, who had the thinnest tumor (0.7 cm) in a series of 10 cases and was the only 1 with invasion limited to submucosa (pT1pN0), survived 108 months after operation being alive and well at the time of the last follow-up.40 Other interesting cases reported with long-term survival, not included in our tabulation, all with T1 tumors, are a Japanese case94 from the recent literature who received repeated endoscopic treatments (EMR) for a pT1cN0 tumor, limited to mucosa who developed liver metastasis after 7 years from diagnosis and was doing well for 1 more year after hepatic transarterial chemoembolization, and a pT1N1 white patient from the early 1990s who was alive and healthy at the time of the report 12 years after excision of tumor.126

Back to Top | Article Outline

ACKNOWLEDGMENTS

The authors wish to thanks Dr M. Carandente and Mrs L. Giuliani, who are affiliated with IRCCS “Casa Sollievo della Sofferenza” Hospital, San Giovanni Rotondo, Italy, for their valuable assistance in the bibliography search during the preparation of the study; Dr M. Fukunaga of the Department of Pathology, The Jikei Daisan Hospital, Komaeshi, Tokyo, Japan, for helping us to obtain full information from studies in Japanese, and Dr D. Ben Dor of the Department of Pathology, The Barzilai Medical Center, Ashkelon, Israel, for his critical review and editing of the study.

This study was presented in abstract form (Poster presentation) at the Annual Italian SIAPEC-IAP Congress of Anatomic Pathology. Bologna, Italy, 21-25 September, 2010.

Back to Top | Article Outline

REFERENCES

1. Batsakis JG, Suarez P. Mucosal melanomas: a review Adv Anat Pathol.. 2000;7:167–180

2. Mills SE, Cooper PH. Malignant melanoma of the digestive system Pathol Annu.. 1983;18:1–26

3. Cheung MC, Perez EA, Molina MA, et al. Defining the role of surgery for primary gastrointestinal tract melanoma J Gastrointest Surg.. 2008;12:731–738

4. Sabanathan S, Eng J, Pradhan GN. Primary malignant melanoma of the esophagus Am J Gastroenterol.. 1989;84:1475–1481

5. Coté TR, Sobin LH. Primary melanomas of the esophagus and anorectum: epidemiologic comparison with melanoma of the skin Melanoma Res.. 2009;19:58–60

6. Volpin E, Sauvanet A, Couvelard A, et al. Primary malignant melanoma of the esophagus: a case report and review of the literature Dis Esophagus.. 2002;15:244–249

7. Taniyama K, Suzuki H, Sakuramachi S, et al. Amelanotic malignant melanoma of the esophagus: case report and review of the literature Jpn J Clin Oncol.. 1990;20:286–295

8. Joob AW, Haines GK III, Kies MS, et al. Primary malignant melanoma of the esophagus Ann Thorac Surg.. 1995l;60:217–222

9. Baur EH. Primary melanoma of the esophagus: a case report Arb Geb Pathol Anat Inst Tubingen.. 1906;5:343–354 [Article in German].

10. Loftus BM, Broe P, Johnston O, et al. Primary amelanotic malignant melanoma of the oesophagus: a case report Ir J Med Sci.. 1994;163:128–131

11. Al-Karawi MA, Mohamed SA, Macdougall C. Primary malignant melanoma of esophagus Ann Saudi Med.. 1994;14:348–350

12. Deligeorgi-Politi H, Kairi-Vassilatou E. Primary malignant melanoma of the esophagus Ann Saudi Med.. 1995;15:293–294

13. Chan HS, Nambiar R. Malignant melanoma of the oesophagus: a case report Singapore Med J.. 1995;36:566–567

14. Kinuya S, Tonami N, Hisada K. Ga-67 SPECT in primary gastroesophageal malignant melanoma Clin Nucl Med.. 1996;21:325–326

15. Simonov NN, Turkevich EA, Gel'fond VM, et al. Primary malignant melanoma of the intrathoracic part of the esophagus [Article in Russian] Vestn Khir Im I I Grek.. 1998;157:71–73

16. Lam KY, Law S, Wong J. Malignant melanoma of the oesophagus: clinicopathological features, lack of p53 expression and steroid receptors and a review of the literature Eur J Surg Oncol.. 1999;25:168–172

17. Kido T, Morishima H, Nakahara M, et al. Early stage primary malignant melanoma of the esophagus Gastrointest Endosc.. 2000;51:90–91

18. Archer HA, Owen WJ. Primary malignant melanoma of the esophagus Dis Esophagus.. 2000;13:320323

19. Gadour MO, Ayoola EA. Primary malignant melanoma of the oesophagus: case report and review Trop Gastroenterol.. 2000;21:185–187

20. Guermazi A, Rili M, Fritsch S, et al. Primary malignant melanoma of the esophagus: a case of early-stage primary malignant melanoma of the esophagus Ann Chir.. 2000;125:985–988

21. Mikami T, Fukuda S, Shimoyama T, et al. A case of early-stage primary malignant melanoma of the esophagus Gastrointest Endosc.. 2001;53:365–367

22. Xinopoulos D, Archavlis EM, Kontou M, et al. Primary melanoma of the oesophagus treated endoscopically: a case report . Dig Liver Dis.. 2001;33:254–257

23. de Perrot M, Bründler MA, Robert J, et al. Primary malignant melanoma of the esophagus Dis Esophagus.. 2000;13:172–174

24. Sagie B, Kashtan H, Kluger Y. Primary malignant melanoma of the esophagus Isr Med Assoc J.. 2000;2:557–558

25. Kastl S, Wutke R, Czeczatka P, et al. Palliation of a primary malignant melanoma of the distal esophagus by stent implantation: report of a case Surg Endosc.. 2001;15:1042–1403

26. Khoury-Helou A, Lozac'h C, Vandenbrouke F, et al. Primary malignant melanoma of the esophagus Ann Chir.. 2001;126:557–560

27. Herman J, Duda M, Lovecek M, et al. Primary malignant melanoma of the esophagus treated by endoscopic ablation and interferon therapy Dis Esophagus.. 2001;14:239–240

28. Matsutani T, Onda M, Miyashita M, et al. Primary malignant melanoma of the esophagus treated by esophagectomy and systemic chemotherapy Dis Esophagus.. 2001;14:241–244

29. Alves A, Maillochaud JH, Sauvanet A, et al. Primary malignant melanoma of the esophagus: value of endoscopic ultrasonography in the assessment of extension Gastroenterol Clin Biol.. 2001;25:1117–1118

30. Cuesta-Mejías T, de León-Bojorge B, Arias-Gutiérrez A, et al. Primary melanoma of the esophagus: unusual case with Barrett's esophagus Rev Gastroenterol Mex.. 2001;66:146–149

31. Lin CY, Cheng YL, Huang WH, et al. Primary malignant melanoma of the oesophagus presenting with massive melena and hypovolemic shock ANZ J Surg.. 2002;72:62–64

32. Boni L, Benevento A, Dionigi G, et al. Primary malignant melanoma of the esophagus: a case report Surg Endosc.. 2002;16:359–360

33. Boni L, Benevento A, Cabrini L, et al. Primary melanoma of the esophagus J Am Coll Surg.. 2002;194:840

34. Holck S, Siemsen M, Jensen DB, et al. Endoscopic ultrasonography-guided fine needle aspiration biopsy for staging malignant melanoma of the esophagus: a case report Acta Cytol.. 2002;46:744–748

35. Benferhat S, Lessourd A, Lévy P, et al. Primary malignant melanoma of the esophagus Gastroenterol Clin Biol.. 2003;27:113–115

36. Sakamoto H, Uedo N, Iishi H, et al. Treatment of primary malignant melanoma of the esophagus with endoscopic injection of interferon-beta combined with systemic chemotherapy: a case report Gastrointest Endosc.. 2003;57:773–777

37. Sudhamshu KC, Kouzu T, Matsutani S, et al. Primary malignant melanoma of the esophagus treated with heavy-ion radiotherapy J Clin Gastroenterol.. 2003;37:151–154

38. Gul YA, Prasannan S, Hairuszah I. Primary malignant melanoma of the oesophagus Acta Chir Belg.. 2003;103:420–422

39. Gao Y, Zhu J, Lin W, et al. Primary malignant melanoma of esophagogastric junction: a case report Chin Med J (Engl).. 2003;116:1435–1437

40. Lohmann CM, Hwu WJ, Iversen K, et al. Primary malignant melanoma of the oesophagus: a clinical and pathological study with emphasis on the immunophenotype of the tumours for melanocyte differentiation markers and cancer/testis antigens Melanoma Res.. 2003;13:595–601

41. Yamaguchi T, Shioaki Y, Koide K, et al. A case of primary malignant melanoma of the esophagus and analysis of 193 patients in Japan Nippon Shokakibyo Gakkai Zasshi.. 2004;101:1087–1094

42. Wayman J, Irving M, Russell N, et al. Intraluminal radiotherapy and Nd:YAG laser photoablation for primary malignant melanoma of the esophagus Gastrointest Endosc.. 2004;59:927–929

43. Fogarty GB, Tartaglia CJ, Peters LJ. Primary melanoma of the oesophagus well palliated by radiotherapy Br J Radiol.. 2004;77:1050–1052

44. Uetsuka H, Naomoto Y, Fujiwara T, et al. Primary malignant melanoma of the esophagus: long-term survival following pre- and postoperative adjuvant hormone/chemotherapy Dig Dis Sci.. 2004;49:1646–1651

45. Patonay P, Naszály A, Mayer A, et al. Radio-chemotherapy for non-resectable primary esophageal malignant melanoma Magy Onkol.. 2004;48:303–308

46. Dabrowski A, Skoczylas T, Misztal B, et al. Diagnostic and therapeutic difficulties in a patient with primary malignant melanoma of the esophagus: case report Pol Merkur Lekarski.. 2004;17:378–379

47. Dabrowski A, Zinkiewicz K, Szumilo J, et al. Unusual clinical course of metachronous melanomas of the upper digestive system World J Gastroenterol.. 2005;11:2197–2199

48. Kimura H, Kato H, Sohda M, et al. Flat-type primary malignant melanoma of the esophagus treated by EMR: case report Gastrointest Endosc.. 2005;61:787–789

49. Asakage M, Kitayama J, Tsuno NH, et al. Primary malignant melanoma of the esophagus treated by esophagectomy and adjuvant dendritic-cell therapy J Gastroenterol.. 2005;40:545–546

50. Suzuki Y, Aoyama N, Minamide J, et al. Amelanotic malignant melanoma of the esophagus: report of a patient with recurrence successfully treated with chemoendocrine therapy Int J Clin Oncol.. 2005;10:204–247

51. Heidemann J, Lebiedz P, Herbst H, et al. Amelanotic malignant melanoma of the esophagus: case report Z Gastroenterol.. 2005;43:597–600

52. Awsare M, Friedberg JS, Coben R. Primary malignant melanoma of the esophagus Clin Gastroenterol Hepatol.. 2005;3:xxvii

53. Stringa O, Valdez R, Beguerie JR, et al. Primary amelanotic melanoma of the esophagus Int J Dermatol.. 2006;45:1207–1210

54. Okano K, Sugiyama T, Akamoto S, et al. (18)F-FDG accumulations in primary malignant melanoma of the esophagus Surgery.. 2006;140:118–119

55. Kakudo Y, Yoshioka T, Noguchi S, et al. A case of malignant melanoma from the esophagus responding to weekly paclitaxel therapy Gan To Kagaku Ryoho.. 2006;33:969–972

56. Vandewoude M, Cornelis A, Wyndaele D, et al. (18)FDG-PET-scan in staging of primary malignant melanoma of the oesophagus: a case report Acta Gastroenterol Belg.. 2006;69:12–14

57. De Simone P, Gelin M, El Nakadi I. Amelanotic malignant melanoma of the esophagus: report of a case Minerva Chir.. 2006;61:45–49

58. Lin PW, Lee RC, Chern MS, et al. Primary malignant melanoma of the esophagus J Chin Med Assoc.. 2006;69:334–337

59. Pruyt M, Devriendt D, Vanneste A. Malignant melanoma and adenocarcinoma of a Barrett oesophagus Acta Chir Belg.. 2006;106:616–618

60. Ueda Y, Shimizu K, Itoh T, et al. Induction of peptide-specific immune response in patients with primary malignant melanoma of the esophagus after immunotherapy using dendritic cells pulsed with MAGE peptides Jpn J Clin Oncol.. 2007;37:140–145

61. Lee SA, Hwang JJ, Choi YH. Surgical treatment of primary malignant melanoma of the esophagus: a case report J Korean Med Sci.. 2007;22:149–152

62. Ho KY, Cheng J, Wee A, et al. Primary malignant melanoma of the esophagus with multiple esophageal lesions Nat Clin Pract Gastroenterol Hepatol.. 2007;4:171–174

63. Gerger A, Smolle-Jüttner FM, Samonigg H, et al. Asymptomatic primary malignant melanoma of the esophagus Onkologie.. 2007;30:206–208

64. Li B, Lei W, Shao K, et al. Characteristics and prognosis of primary malignant melanoma of the esophagus Melanoma Res.. 2007;17:239–242

65. Kelly J, Leader M, Broe P. Primary malignant melanoma of the oesophagus: a case report J Med Case Reports.. 2007;1:50

66. Oshiro T, Shimoji H, Matsuura F, et al. Primary malignant melanoma of the esophagus arising from a melanotic lesion: report of a case Surg Today.. 2007;37:671–675

67. Solari N, Acquati M, Queirolo P, et al. Primary melanoma of the esophagus with non-metastatic dark lymph nodes in a female breast cancer patient Anticancer Res.. 2007;27:2849–2853

68. de Bruin GJ, Mulder AH, Witteman BJ. Primary malignant melanoma of the gastrointestinal tract: a case report and review of the literature Acta Gastroenterol Belg.. 2007;70:367–370

69. Kanamori N, Igaki H. A case of primary malignant melanoma of the esophagus Jpn J Clin Oncol.. 2008;38:233

70. Frangi Caregnato A, Alvarez Martínez D, Montalva Orón E, et al. Primary melanoma of the esophagus Cir Esp.. 2008;83:325

71. Suzuki H, Nakanishi Y, Taniguchi H, et al. Two cases of early-stage esophageal malignant melanoma with long-term survival Pathol Int.. 2008;58:432–435

72. Wang S, Thamboo TP, Nga ME, et al. C-kit positive amelanotic melanoma of the oesophagus: a potential diagnostic pitfall Pathology.. 2008;40:527–530

73. Leong QM, Kam JH. Primary malignant melanoma of the lower oesophagus presenting with dysphagia and upper gastrointestinal bleeding Cases J.. 2008;1:28

74. Sanchez AA, Wu TT, Prieto VG, et al. Comparison of primary and metastatic malignant melanoma of the esophagus: clinicopathologic review of 10 cases Arch Pathol Lab Med.. 2008;132:1623–1629

75. Fredricks JR, Bejarano PA. Primary malignant melanoma of the esophagus with separate foci of melanoma in situ and atypical melanocytic hyperplasia in a patient positive for human immunodeficiency virus: a case report and review of the literature Arch Pathol Lab Med.. 2008;132:1675–1678

76. Tzung-Ju L, Tsai-Wang H, Shih-Chun L. Primary malignant melanoma of the esophagus Ann Saudi Med.. 2008;28:458–460

77. Zhuang YZ, Zhang ZY, Liao YQ. Primary malignant melanoma of esophagus: report of a case Zhonghua Bing Li Xue Za Zhi.. 2009;38:60–61

78. Terada T. Amelanotic malignant melanoma of the esophagus: report of two cases with immunohistochemical and molecular genetic study of KIT and PDGFRA World J Gastroenterol.. 2009;15:2679–2683

79. Rivera Irigoín R, Aguilar Urbano V, Gonzalo Marín J, et al. Primary esophageal melanoma Rev Gastroenterol Peru.. 2009;29:185–190

80. Kang MJ, Yi SY. Nevus-like appearance of primary malignant melanoma of the esophagus Gastroenterol Res Pract.. 2009;2009:285753

81. Gupta V, Kochhar R, Sinha SK, et al. Primary malignant melanoma of the esophagus: long-term survival after radical resection J Thorac Oncol.. 2009;4:1180–1182

82. Mamori S, Kahara F, Ohnishi K, et al. Survivin expression in primary malignant melanoma of the esophagus Scand J Gastroenterol.. 2009;44:1497–1498

83. Houissa F, Bouzaidi S, Mouelhi L, et al. Diffuse primary malignant melanoma of the upper gastrointestinal tract Gastroenterol Clin Biol.. 2010;34:85–87

84. Nonoshita T, Shioyama Y, Nomoto S, et al. Effective palliative radiotherapy in primary malignant melanoma of the esophagus: a case report Cases J.. 2009;2:6928 doi: 10.4076/1757-1626-2-6928.

85. Yang X, Qu J, Wang S. Primary malignant melanoma of the esophagus Melanoma Res.. 2010;20:59–60

86. Frieling T, Heise J, Hemmerlein B. Image of the month. Primary malignant melanoma of the esophagus Clin Gastroenterol Hepatol.. 2010;8:A22

87. Butte JM, Visscher A, De La Fuente H, et al. Esophageal melanoma: report of two cases Rev Med Chil.. 2010;138:77–81

88. Fujii K, Goto A, Matsunaga Y, et al. Primary malignant melanoma of the esophagus—detection of circulating tumor cells Gan To Kagaku Ryoho.. 2010;37:1539–1543

89. Dionigi G, Rovera F, Boni L, et al. Solitary pulmonary metastasis from primary melanoma of the oesophagus 5 years after resection of the primary tumor World J Surg Oncol.. 2006;4:22

90. Sunayama K, Takagi M, Kobayashi K, et al. A long term survival case of esophageal primary malignant melanoma with melanocytic hyperplasia and intramural metastases: a case report Jpn J Gastroenterol Surg.. 2000;33:186–190

91. Nomura T, Onda M, Miyashita M, et al. Transhiatal esophagectomy assisted by mediastinoscopy for primary malignant melanoma of esophagus: a case report [in Japanese with English abstract] J Jpn Surg Assoc.. 2002;63:1157–1161

92. Hirose T, Yoshida M, Katoh H, et al. Malignant melanoma of the esophagus, report of a case [in Japanese with English abstract] Stomach and Intestine (Tokyo). 2002;37:1361–1365

93. Hara S, Noguchi M, Sugiyama K, et al. A case of primary malignant melanoma of the esophagus in situ [in Japanese with English abstract] Gastroenterol Endosc. 2003;45:935–939

94. Morita S, Miyamoto S, Matsumoto S, et al. Multiple early-stage malignant melanoma of the esophagus with long follow-up period after endoscopic treatment: report of a case Esophagus. 2009;6:249–252

95. Li ZY, Cai JQ, Cui XZ, et al. Outcome of malignant melanoma in gastrointestinal tract: clinical analysis of 70 cases Zhonghua Wai Ke Za Zhi.. 2008;46:574–576

96. Walter A, van Rees BP, Heijnen BH, et al. Atypical melanocytic proliferation associated with squamous cell carcinoma in situ of the esophagus Virchows Arch.. 2000;437:203–207

97. De la Pava S, Nigogosyan G, Pickren JW, et al. Melanosis of the esophagus Cancer.. 1963;16:48–50

98. Tateishi R, Taniguchi H, Wada A, et al. Argyrophil ceIls and melanocytes in esophageal mucosa Arch Pathol.. 1974;98:87–89

99. Ohashi K, Kato Y, Kanno J, et al. Melanocytes and melanosis of the oesophagus in Japanese subjects: analysis of factors effecting their increase Virchows Arch A Pathol Anat Histopathol.. 1990;417:137–143

100. Basque GJ, Boline JE, Holyoke JB. Malignant melanoma of the esophagus: first reported case in a child Am J Clin Pathol.. 1970;53:609–611

101. Yoshikane H, Suzuki T, Yoshioka N, et al. Primary malignant melanoma of the esophagus presenting with massive hematemesis Endoscopy.. 1995;27:397–399

102. Yano M, Shiozaki H, Murata A, et al. Primary malignant melanoma of the esophagus associated with adenocarcinoma of the lung Surg Today.. 1998;28:405–408

103. Yamasaki M, Kitamura S, Higuchi M. Case of synchronous quadruple cancer (esophageal melanoma, gastric cancer, colonic cancer and bladder cancer) Gan No Rinsho.. 1969;155:501–507

104. Brown RM, Darnton SJ, Papadaki L, et al. A primary tumour of the oesophagus with both melanocytic and schwannian differentiation.: Melanocytic schwannoma or malignant melanoma? J Clin Pathol.. 2002;55:318–320

105. Isabel ZY, Fitzpatrick JE. Expression of c-kit (CD117) in Spitz naevus and malignant melanoma J Cutan Pathol.. 2006;33:33–37

106. Frable WJ, Kay S, Schatzki P. Primary malignant melanoma of the esophagus: an electron microscopic study Am J Clin Pathol.. 1972;58:659–667

107. Go AT, Zirkin RM. Primary malignant melanoma of the esophagus: a case report with endoscopic and electron microscopic studies Am J Gastroenterol.. 1982;77:840–843

108. Sharma SS, Venkateswaran S, Chacko A, et al. Melanosis of the esophagus: an endoscopic, histochemical, and ultrastructural study Gastroenterology.. 1991;100:13–16

109. Chang F, Deere H. Esophageal melanocytosis morphologic features and review of the literature Arch Pathol Lab Med.. 2006;130:552–557

110. Chang F. Melanocytosis of the oesophagus: a case report Pathology.. 2006;38:83–85

111. Piccone VA, Klopsrock R, LeVeen HR, et al. Primary malignant melanoma of the esophagus associated with melanosis of the entire esophagus J Thorac Cardiovasc Surg.. 1970;59:864–870

112. Schneider A, Martini N, Burt ME. Malignant melanoma metastatic to the esophagus Ann Thorac Surg.. 1993;55:516–517

113. Bogomoletz WV, Lecat M, Amoros F. Melanosis of the oesophagus in a Western patient Histopathology.. 1997;30:498–499

114. Kanavaros P, Galian A, Periac P, et al. Primary malignant melanoma of the esophagus arising in melanosis: histological, immunohistochemical and ultrastructural study of a case Ann Pathol.. 1989;9:57–61

115. Muto M, Saito Y, Koike T, et al. Primary malignant melanoma of the esophagus with diffuse pigmentation resembling superficial spreading melanoma Am J Gastroenterol.. 1997;92:1936–1937

116. Guzman RP, Wightman R, Ravinsky E, et al. Primary malignant melanoma of the esophagus with diffuse melanocytic atypia and melanoma in situ Am J Clin Pathol.. 1989;92:802–804

117. Horowitz M, Nobrega MM. Primary anal melanoma associated with melanosis of the upper gastrointestinal tract Endoscopy.. 1998;30:662–665

118. Murata T, Imai T, Hoshino K, et al. Esophageal anthracosis: lesion mimicking malignant melanoma Pathol Int.. 2002;52:488–491

119. Blecker D, Abraham S, Furth EE, et al. Melanoma in the gastrointestinal tract Am J Gastroenterol.. 1999;94:3427–3433

120. Fanning J, Alvarez PM, Tsukada Y, et al. Cervical implantation metastasis by endometrial adenocarcinoma Cancer. 1991;68:1335–1339

121. Cadili A. Primary melanoma of the esophagus: a rare and challenging problem South Med J.. 2009;102:883–884

122. Caldwell CB, Bains MS, Burt M. Unusual malignant neoplasms of the esophagus.: Oat cell carcinoma, melanoma, and sarcoma J Thorac Cardiovasc Surg.. 1991;101:100–107

123. Chalkiadakis G, Wihlm JM, Morand G, et al. Primary malignant melanoma of the esophagus Ann Thorac Surg.. 1985;39:472–475

124. Naomoto Y, Perdomo JA, Kamikawa Y, et al. Primary malignant melanoma of the esophagus: report of a case successfully treated with pre- and post-operative adjuvant hormone-chemotherapy Jpn J Clin Oncol.. 1998;28:758–761

125. Namieno T, Koito K, Ambo T, et al. Primary malignant melanoma of the esophagus: diagnostic value of endoscopic ultrasonography Am Surg.. 1996;62:716–718

126. Hamdy FC, Smith JHF, Kennedy A, et al. Long survival after excision of a primary malignant melanoma of the oesophagus Thorax. 1991;46:397–398

Cited By:

This article has been cited 3 time(s).

Annals of Thoracic Surgery
Diagnosis and Surgical Outcomes for Primary Malignant Melanoma of the Esophagus: A Single-Center Experience
Wang, SH; Tachimori, Y; Hokamura, N; Igaki, H; Kishino, T; Kushima, R
Annals of Thoracic Surgery, 96(3): 1002-1007.
10.1016/j.athoracsur.2013.04.072
CrossRef
Gastroenterology
A Rare but Unique Tumor in the Esophagus Answer to the Clinical Challenges and Images in GI: Image 2 (page 695): Primary Esophageal Melanoma
Wu, IC; Lee, JY; Wu, CC
Gastroenterology, 144(4): 695-+.
10.1053/j.gastro.2012.11.004
CrossRef
World Journal of Surgical Oncology
Primary malignant melanoma of the esophagus: a rare and aggressive disease
Morita, FHA; Ribeiro, U; Sallum, RAA; Tacconi, MR; Takeda, FR; da Rocha, JRM; Ligabo, GDC; de Melo, ES; Pollara, WM; Cecconello, I
World Journal of Surgical Oncology, 11(): -.
ARTN 210
CrossRef
Back to Top | Article Outline
Keywords:

melanoma; esophagus; immunohistochemistry; electronmicroscopy

© 2011 Lippincott Williams & Wilkins, Inc.

Login

Article Tools

Images

Share

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.