Undifferentiated small cell carcinoma (SCC) is an aggressive lung tumour accounting for 15% of all lung cancers [1
]. Extrapulmonary small cell carcinomas (ESC) in comparison are rare with an incidence between 0.1–0.4% of all cancers [2
]. Approximately 2.5% of all SCC's arise in extrapulmonary sites such as the salivary glands, pharynx, larynx, nasal sinuses, pancreas, oesophagus, colon, rectum, skin and cervix [2
]. Colorectal ESCs are rare with an incidence of 0.3% of all colorectal cancers and like SCC of the lung, are aggressive malignancies with early metastasis and have an overall 5-year survival of 13% [6
]. Kim et al
(2004) reported a 12.5% incidence of colorectal ESC with 3 patients affected from a retrospective review of 24 patients with ESC [7
Age and sex distribution for ESC are similar to that seen in adenocarcinoma of the colon [6
]. Although smoking is clearly implicated in the formation of pulmonary SCC, its association with ESC is not clearly documented. This patient was a non-smoker but there was a family history of lung cancer with an elderly brother who died in his fifties. The type of lung cancer affecting the patient's brother was not determined and therefore it is unclear whether her family history of lung cancer had a causative role either.
SCC is thought to originate from neuroendocrine cells, which are found in the epithelium of many mucosal surfaces including the gastrointestinal tract [6
]. Despite evidence of neuroendocrine involvement, the origin of ESC is still unclear as development from undifferentiated airway epithelium has also been suggested along with the amine precursor uptake and decarboxylation (APUD) system hypothesis which proposes a common ancestral cell derived from the neural crest, which then migrates to various epithelial tissues and sites within the body [8
Histopathological diagnosis can be confirmed by the classic appearance of small round to oval shaped cells with a finely granular and hyperchromatic nucleus, inconspicuous nucleoli and scanty cytoplasm on light microscopy [8
]. SCC's show a strong and diffuse immunoreactivity for CD 56 and 80% positivity for TTF-1 tumour markers [10
]. TTF-1 is positive in most cases of pulmonary small cell carcinoma, but also shows positive staining with many high-grade neuroendocrine carcinomas of non-pulmonary origin. The importance of TTF-1 is to exclude metastatic Merkel cell carcinoma, which is TTF-1 negative [11
]. Due to the extent of disease in our case it was not possible to assess dysplastic changes of the surrounding mucosa. In the absence of a lung primary combined with the immunohistochemical profile of the appendiceal tumour suggests that this patient had a pure extrapulmonary SCC of her appendix. Although carcinoid tumours account for 32–35% of all appendiceal neoplasms, SCC's of the appendix are rarer with only one previously reported case by Rossi et al
and this was mixed with adenocarcinoma [12
]. To the authors' knowledge this is the first reported case of a pure small cell carcinoma of the appendix. Further investigative modalities with CT imaging and bronchoscopy are mandatory to exclude a pulmonary origin [2
]. Although this patient had a positive family of pulmonary neoplasia, she was a non-smoker with no respiratory symptomatology and had a normal chest CT scan. Following consultation with the respiratory department following surgery, no further investigation was requested as oncological treatment was the priority.
Unfortunately clinical presentation of ESC carcinoma is usually at an advanced stage due to the aggressive nature of the disease. Therapeutic modalities are determined by the location and extent of disease. Chemotherapy remains the treatment of choice. The role of radiotherapy and surgical intervention remain limited, with surgery often only being used for the treatment of localised disease [15
]. Combination chemotherapy regimens using cisplatin-etoposide are the most commonly used with response rates of up to 70% [4
]. There are no definite chemotherapeutic regimens for ESC of the colon due to the small patient numbers and clinically advanced disease at presentation.
The prognosis for ESC is similar to pulmonary SCC's and remains poor with a rapidly deteriorating clinical course. Five-year survival is less than 13% [15
]. The mean survival for gastrointestinal ESC is less than 5-months with a 3- and 8-month mean survival for extensive and localised disease respectively [16