Melanocytosis of the oesophagus: a case report

Melanocytosis of the oesophagus: a case report

CORRESPONDENCE Melanocytosis of the oesophagus: a case report Sir, Oesophageal melanocytosis, also called melanosis, is a rare condition, being found...

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Melanocytosis of the oesophagus: a case report Sir, Oesophageal melanocytosis, also called melanosis, is a rare condition, being found in 0.07–2.1% of consecutive gastrointestinal endoscopies.1–10 So far approximately 30 cases have been reported, of which 21 cases were reported in an Indian series4 and four cases in a Japanese series.3 Very few cases are from Western populations.5,6 Due to its uncommon nature, many pathologists lack experience with this entity. We describe here a typical case of oesophageal melanocytosis in an 80-year-old English Caucasian woman presenting with bluish-black macules in her distal oesophagus. The patient underwent upper gastrointestinal endoscopy because of dysphagia and epigastric pain. Her past health was unremarkable except for hypertension and osteoporosis. No family history of any syndromes was identified. She was a non-smoker and there was no history of fever, jaundice, weight loss or anorexia in the past. Examination of the skin, oral cavity and ano-genital region disclosed no significant abnormality. On CT scan, the liver, spleen, adrenals, pancreas, and kidneys were unremarkable. Basic laboratory tests, including white blood cell count, haemoglobin, renal, and liver function tests, were all within normal range.


Conventional endoscopy demonstrated multiple bluish and dark-brown, flat, irregularly delineated mucosal macules in the distal oesophagus 30–34 cm from the incisor teeth. This area measured 40 mm in length and 25 mm in width. The rest of the oesophagus, stomach, and duodenum were grossly unremarkable. Colonoscopy revealed diverticular disease and, in addition, a small polyp in the sigmoid colon. No tumour masses were detected in the gastrointestinal tract. Multiple biopsies were taken from the pigmented areas. H&E sections showed increased numbers of pigment-laden dendritic melanocytes and deposition of coarse brownishblack pigment within the basal layer of the squamous epithelium (Fig. 1A). These cells were positive for S100 (Fig. 1B) and HMB45. The melanocytes did not exhibit any sign of nuclear or cellular atypia. The underlying lamina propria contained numerous pigment-laden macrophages (Fig. 2A). The pigment stained positive with the MassonFontana method (Fig. 2B), was bleached completely with hydrogen peroxide and was negative with both periodic acid-Schiff (PAS) and Perls’ methods. The pigment-laden cells in the lamina propria were positive for CD68 (Fig. 2C), but negative for S100, Melan A and HMB45 (Fig. 2D). The overlying squamous epithelium was slightly thickened, but demonstrated mature differentiation. There was mild lymphoplasmacytic inflammatory infiltration and fibrosis with areas of telangiectasia in the lamina propria. Biopsies of duodenal mucosa demonstrated normal tissue architecture and biopsies of gastric mucosa showed mild chronic antral gastritis without Helicobacter-like organisms. The small polyp identified by colonoscopy was histologically a tubular adenoma with moderate dysplasia. The large bowel mucosa was otherwise unremarkable. There was no evidence of melanoma or other malignancies in any of these gastrointestinal biopsies. Histological appearances and the special staining results are consistent with oesophageal melanocytosis. At follow-up

Fig. 1 Oesophageal melanocytosis. (A) H&E section showing increased numbers of pigment-laden dendritic melanocytes and deposition of melanin pigment in the basal layer of the squamous epithelium (6400). (B) Intraepithelial melanocytes are positive for S100 (6200).



endoscopy (6 months after the diagnosis), there was no remarkable change in the pigmented areas of the oesophagus. Oesophageal melanocytosis is a rare, benign condition defined as increased numbers of melanocytes in the basal layer of oesophageal squamous epithelium and an increased quantity of melanin in oesophageal mucosa. So far about 30 cases have been reported, 1–10 the majority of which were from Indian4 and Japanese populations.3 Very few cases were from Western countries.5,6 Overall, oesophageal melanosis was more commonly seen in men and mainly in the middle and lower third of the oesophagus. Endoscopically, oesophageal melanocytosis has been described as flat, oval, and irregularly delineated lesions. Magnifying endoscopy disclosed that the pigmented area consisted of granule-like spots and linearly arranged granules.8 Biopsy specimens confirm that the pigmentation in the tissue is composed of melanocytes in the basal layer of the squamous epithelium

Pathology (2006), 38(1), February

and the melanin-laden macrophages (melanophages) in the subepithelial connective tissue.1–10 Similar to the melanin seen elsewhere, the pigment is positive with Masson-Fontana staining and is negative with Perls’ iron staining. This pigment can be bleached with hydrogen peroxide. Electron microscopy shows the presence of dendritic melanocytes with melanosomes in various stages of development in the basal layer of the oesophagea1 epithelium.3 The origin of melanocytes in the oesophagus remains uncertain. Some authors suggested that these cells arise in the neural crest and migrate to the oesophageal mucosa, in the same way in which they migrate to the skin and other sites including uvea, choroid, leptomeninges, substantia nigra, oral cavity and nasopharynx.1–4,11 An alternative possibility is that melanocytes are formed in the oesophagus as the result of differentiation from the stem cells in the basal layer of the squamous epithelium.5

Fig. 2 Oesophageal melanocytosis. (A) Numerous pigment-laden macrophages are present in the subepithelial lamina propria (6200). (B) The pigment stains positive with the Masson-Fontana method (6400). (C) The pigment-laden cells (melanophages) are positive for CD68 (6400), but (D) negative for S100 (6200).


An increase in the number of melanocytes is well recognised to occur in skin in response to noxious stimuli, however, little is known about the aetiological factors and pathogensis of oesophageal melanocytosis. Chronic stimulus, such as gastro-oesophageal reflux disease, that causes mucosal damage and keratinocytic hyperplasia, could be capable of causing increased melanosis.2 In the current case, chronic oesophagitis was noted histologically, which could pose a contributing factor for the hyperpigmentation. Oesophageal melanosis or melanocytosis has also been associated with a variety of systemic disorders, such as Peutz–Jeghers syndrome, Laugier–Hunziker syndrome and Addison’s disease.9,10 Notably, endoscopic or macroscopic melanosis has been described in 25%–30% of surgical specimens of the oesophagus containing primary malignant melanomas; thus, this lesion has been suggested to be a precursor of melanoma by some authors.12,13 However, no follow-up information or direct evidence of malignant transformation of oesophageal melanocytosis is currently available. Oesophageal melanosis must be differentiated from melanoma and benign naevi, because melanin deposition is often the main feature in these lesions. Primary melanoma of the oesophagus is uncommon, accounting for 0.1–0.4% of oesophageal malignancies.12,13 Endoscopically, it often presents as pigmented or non-pigmented polypoid mass in the middle or lower oesophagus. Histologically, melanoma is composed of epithelioid cells arranged in nests or spindle cells with prominent nucleoli and nuclear atypia. A single case of oesophageal blue naevus was recently reported by Lam et al.14 from a 52-year-old Chinese woman who presented with linear patches of bluish pigmentation in her lower oesophagus. Similar to its cutaneous counterparts, this is characterised by the presence of dendritic melanocytes in the subepithelial connective tissue without junctional melanocytic activity. The absence of cytological atypia and the presence of heavily pigmented dendritic melanocytes in stromal tissue differentiate the lesion from melanoma and melanocytosis. In addition, endoscopic differential diagnoses of oesophageal melanocytosis should theoretically include anthracosis, exogenous dye ingestion, haemosiderosis and lipofuscin deposition (pseudomelanosis).15,16 These lesions could be easily excluded after histological and histochemical examination. A dark-pigmented oesophageal mucosa, the so-called ‘black oesophagus’ is a rare observation during upper endoscopy.15 It appears endoscopically as a darkpigmented oesophagus with ulcerations which corresponds to severe acute inflammation with mucosal necrosis seen on histological examination.15 The aetiological factor involved seems to be ischaemic injury caused by arteriolosclerosis, arterial thrombosis, or aortic dissection.15 Blue rubber bleb naevus syndrome is also a rare condition characterised by the presence of multiple bluish, slightly raised angiomatous lesions of the skin and the gastrointestinal tract, causing anaemia through chronic bleeding.16 Histologically, these lesions are characterised by a variety of vascular alterations, ranging from capillary telangiectasias to cavernous haemangioma with arteriovenous communication, the latter being the most common finding. In both black oesophagus and blue rubber bleb naevus, haemosiderin pigment and siderophages may be present, but melanocytes and melanin pigment are not seen.15,16


Fuju Chang Department of Histopathology, St Thomas’ Hospital, Guy’s and St Thomas’ NHS Foundation Trust, London, UK Contact Dr F. Chang. E-mail: [email protected] ACKNOWLEDGEMENT The author wishes to acknowledge the skilful technical assistance of Mr K. Marsden (MLSO) and Dr Harriet Deere for reviewing this manuscript.

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DOI: 10.1080/00313020500468889