Two Cdx homeobox genes have been identified so far in humans [1, 2]. CDX-2 is the product of the Cdx-2 homeobox gene and is expressed in normal colonic epithelia and most colorectal adenocarcinomas. Lung and pleural neoplastic lesions require the distinction between primary and metastatic malignancy when occurring alone. Colorectal carcinoma (CRC) must be included in the differential diagnosis as it is one of the most frequent neoplasms giving rise to metastases to the lung. We describe two clinical cases in which CDX-2 was of primary importance to define the colonic origin. A 63-year-old man with a symptomatic right pleural effusion underwent thoracic computed tomography (CT) scan that described an ipsilateral pleural thickening, without adenopathies and lung lesions. Several cytological examinations of the sputum were negative. Total-body FDG PET scan showed right basal pleural uptake alone. Thoracoscopy revealed multiple small nodular localizations in the right pleura and lung. The pleural extemporary histologic examination indicated a mesothelioma, whereas the definitive one reported an adenocarcinoma. TTF-1 expression was negative and CK20 positive. CDX-2 positivity prompted us to carry out a colonoscopy which showed a right colon neoplasia, histologically typified as adenocarcinoma. FOLFIRI regimen was proposed. An asymptomatic 54-year-old man with a neoplastic lesion in the lower lobe of the left lung, casually detected with a routine chest X-ray, underwent a total-body CT scan that did not show any other signs of neoplasia. Fine-needle aspiration biopsy of the lesion was positive for adenocarcinoma. Since the pathologist could not be sure about the lung origin on the basis of morphologic examination alone, the patient underwent gastroscopy and colonoscopy, which showed an ulcer in the antrum and an infiltrating lesion in the right colon, respectively. Histologically both lesions were adenocarcinomas. Though the origin of the lung lesion was not definable with certainty, the patient firstly underwent lung lobectomy and then subtotal gastrectomy and concurrent right hemicolectomy. Histology was (i) lung metastasis of digestive tract adenocarcinoma, CDX-2 positive and TTF-1 negative, pN0, (ii) gastric adenocarcinoma of intestinal type, G2 pT1 pN0, and (iii) colic adenocarcinoma, G2 pT3 pN0, respectively. Colon-oriented chemotherapy was proposed. Histologic features are often inadequate to distinguish between primary and metastatic lung malignancies. Some immunohistochemistry patterns could be useful. At present, only thyroid transcription factor-1 (TTF-1) for lung origin, and cytokeratin 7 and 20 (CK7/CK20) co-expression pattern for colonic origin are available. Nevertheless, TTF-1 is expressed in most but not all lung adenocarcinomas, its sensitivity being reported to be low in some subgroups of pulmonary mucinous adenocarcinomas and in mucinous bronchioloalveolar carcinomas . Moreover, although characteristic for colorectal origin, the CK7–/CK20+ profile is not 100% specific , whereas CDX-2 is highly specific. It has been reported to identify all cases of colorectal metastases to the lung, without any false-negatives or false-positives . Therefore, it is a reliable, specific and sensitive immunohistochemical marker of the neoplastic intestinal epithelium, and it can be easily applied to routine histological and cytological material. Our experience prompted us to recommend that CDX-2 should be included in the work-up of lung and/or pleural neoplastic lesions of undefined origin, as it could guide the therapeutic plan.
|Titolo:||CDX-2 should be included in the work-up of patients with lung metastases from unknown primary|
|Settore Scientifico Disciplinare:||Settore MED/18 - Chirurgia Generale|
|Data di pubblicazione:||dic-2004|
|Digital Object Identifier (DOI):||10.1093/annonc/mdh482|
|Appare nelle tipologie:||01 - Articolo su periodico|