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Carcinoid tumours are uncommon neuroendocrine neoplasms that may be found anywhere in the body but are most commonly seen in the gastro-intestinal and respiratory tracts. Metastasis to the skin occurs in a small proportion of these but primary cutaneous carcinoid tumours are exceedingly rare. There have been five previous cases of primary carcinoid tumours occurring in the skin. To our knowledge, this is the first report of metastasis from a primary cutaneous carcinoid tumour.
Carcinoid tumours are uncommon neuroendocrine tumours that may arise within any tissue of the body. Currently they are thought to arise from cells of the dispersed neuroendocrine system (DNS).
They are most commonly found within the gastro-intestinal and respiratory tract and usually follow an indolent course. However, some tumours, particularly the larger ones, may metastasise to liver or regional lymph nodes.
but none in which metastasis from a primary skin carcinoid has been described.
1. Case report
A 70-year-old lady was referred by her GP to the plastic surgery service in Plymouth with a lesion on her scalp. The GP attempted to biopsy the lesion, thinking it was a sebaceous cyst but found it to be a hard mass. The pathology report diagnosed an adnexal tumour of skin or possibly a metastasis from a lobular breast carcinoma. No such primary was located; she was otherwise well, although taking diuretic for lower limb oedema.
Excision was performed of the 3×3 cm2 lesion for tissue diagnosis, along with an excision biopsy of a lymph node from her occiput. This node had appeared subsequent to her initial presentation. The pathologist reported a tumour of neuroendocrine cells with carcinoid-like growth patterns (Fig. 1, Fig. 2) . The cells were positive for chromogranin, neurone specific enolase, synaptophysin, cytokeratin and CEA (carcinoembryonic antigen) (Fig. 3, Fig. 4) . They were negative for EMA (epithelial membrane antigen, clone E29), HMFG-2 (human milk fat globulin) and PGP 9.5 (protein gene product). The appearances were of a carcinoid (neuroendocrine) tumour. The lymph node consisted entirely of metastatic carcinoid tumour of similar appearance to the main lesion. No further surgery was planned and follow-up was planned on a 3–4 monthly basis (Fig. 5, Fig. 6) .
Fig. 1Slide (low power) showing original carcinoid tumour in skin.
Four years later, she was noted to have a small mobile swelling in the right posterior triangle of her neck. This was treated by excision biopsy and was found to be a further metastasis of the carcinoid tumour. A further mass was found in the same region two years later, which also proved to be metastatic carcinoid with signs of extranodal spread.
Recent investigation of the patient by an Octreotide scan has shown no sites of visceral metastasis and also no sign of an occult primary tumour. Some uptake in the sites of previous excision was noted.
2. Discussion
Oberndorfer first used the term ‘karzinoide’ in 1907 to describe similar tumours that appeared to behave in a more indolent fashion than typical adenocarcinoma. Their incidence is approximately 1.5 per 100,000 population and generally carcinoid tumours have a good prognosis. They are currently thought to arise from neuroendocrine cells in different sites of the body that are linked by a common neuroendocrine phenoype, originating from pluripotent cells that differentiate locally under factors unique to a specific site or organ. This is known as the DNS theory.
They may arise in many organs but most commonly the gut (90%), particularly the appendix and ileum. Appendiceal carcinoids account for approximately half of the cases. Other common locations include the bronchus and ovary. Small bowel carcinoids tend to present in the fifth decade, and all have the potential to metastasise, although the risk depends on the site of the primary and the size of the tumour. Appendiceal carcinoids have a 2% risk of metastasis whereas the small bowel cases have a 35% risk.
Macroscopically, carcinoids are solid tumours with either a yellow tan appearance, reflecting a high lipid content or a red appearance depending upon the degree of vascularity. Histologically, the tumours are composed of a monotonous cell population showing an organoid growth pattern, that may be trabecular, palisaded, glandular, follicular, rosette-like or papillary. Typically the cells are cuboidal and eosinophilic with central nuclei. The nuclei have a finely granular chromatin pattern. Nucleoli are inconspicuous in most typical carcinoids but may be seen in atypical carcinoids. The tumour cells may have an infiltrative growth pattern and some tumours may consist of spindle cells. The associated stroma may show amyloid deposition, calcification or ossification. Ulrastructurally the tumour cells contain numerous dense core granules. Their staining properties are characteristic; taking up potassium citrate and silver, reducing the latter, and thus earning the names enterochromaffin and argentaffin. Both hormonal and neuroendocrine markers can be detected by immunohistochemistry. Carcinoid tumours synthesise 5-hydroxytryptamine, which can be stained for and is pathognomonic for the tumour. Aside from 5-HT, carcinoid tumours produce prostaglandins, substance P, somatostatin, corticotrophin and neuron-specific enolase.
Definitive diagnosis is made histologically by microscopy and specific histochemical and immunohistochemical staining. Tumour cells are characterised by positive reactions to silver stains, and to markers of neuroendocrine differentiation, including neuron-specific enolase, synaptotrypsin, and chromogranin,
Carcinoid tumours express somatostatin receptors and octreotide is a synthetic analogue. Nuclear medicine scanning with radio-labelled octreotide will pick up 90% of tumours.
The carcinoid syndrome includes symptoms of flushing, diarrhoea and wheezing. Since endocrine secretions from a primary tumour in the bowel are subject to first pass metabolism in the liver, the syndrome is not experienced. However, in the case of nonbowel primaries or liver metastases from bowel primaries the hormones are not cleared and so the syndrome may become evident.
The patient never had any of the symptoms of carcinoid syndrome.
Treatment of the primary tumours is by wide local resection. Treatment of metastasis is also by resection if possible. Liver resections are performed to eradicate tumours and there is some experience with liver transplantation, although recurrence is common.
The prognosis of the tumours is generally good. The five-year survival of patients with local disease in the appendix is 94% and for small bowel (65%). For patients with metastases, the figure is around 35% for both.
Carcinoid tumours have been reported to metastasise to skin occasionally. Rodriguez commented that it is rare and may be derived from any primary site. Metastases to the skin from a visceral primary tumour are usually multiple.
The clinical evidence to support this particular tumour being a primary cutaneous lesion is that no other candidate for a primary has been identified in the six-year interval between initial presentation and recent negative octreotide scan.
Although this case has several similarities with previous reported cases of primary skin carcinoid tumours none of the foregoing cases have metastasised. All previously reported tumours were on trunk or scalp and were 10–40 mm in diameter. Immunohistochemical study showed that positive staining was found for chromogranin and keratin markers. All cases had a long history with some years elapsed between diagnosis and the case report. Thus, the tumours seem to have a relatively good prognosis.
This report is the first describing metastasis from a primary cutaneous carcinoid. In summary, this lesion albeit very rare, should be remembered as an uncommon differential diagnosis of a cutaneous mass lesion.
References
Pearse A.G.
Takor T.
Embryology of the diffuse neuroendocrine system and its relationship to the common peptides.
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