Serrated epithelial colorectal polyps (hyperplastic polyps, sessile serrated adenomas) with perineurial stroma: Clinicopathological and molecular analysis of a new series.

Serrated colorectal fibroblastic polyps (FPs) are rare benign mucosal lesions composed of serrated epithelial crypts separated and distorted by intimately associated bland spindle cell proliferations with perineurial-like phenotype. We herein describe 21 new FPs affecting 10 females and 9 males aged 45 to 80 yrs. (mean, 62 yrs). Lesions originated in the sigmoid colon/rectosigmoid junction (n = 16), rectum (n = 2), and other parts of the colon (n = 3). Most patients had additional synchronous or metachronous polyps: classical adenomas (12 patients), sessile serrated adenoma/SSA (1 patient), hyperplastic polyps/HPs (7 patients), both HPs and adenomas (6 patients) and colorectal cancer (2 patients). Size of the lesions varied from 1 to 6 mm (mean: 3 mm). Histologically, all lesions were composed of serrated epithelial crypts that were separated and distorted by spindle cell stromal proliferations (consistently EMA+, claudin-1+ and GLUT-1+). The epithelial component displayed features of HPs (n = 17) and SSA (n = 4). Laser-microdissection-guided molecular testing was successful for 13 epithelial and 9 stromal components (9 paired samples). The BRAF V600E mutation was detected in 54% of the epithelial but in none of the stromal components. In conclusion, colorectal FPs represent genuine serrated epithelial polyps corresponding either to HP or (less frequently) SSA and should be better classified as such with a note on the presence of the stromal component. A more concise terminology reflecting their epithelial nature is needed to fulfill the requirements for colorectal cancer risk assessment and hence adopt appropriate follow-up strategies.

Colorectal Carcinoma With Sarcomatoid Components: Report of 15 Cases and Literature Review of an Exceedingly Rare Carcinoma Subtype.

Colorectal carcinoma with sarcomatoid components (which includes so-called carcinosarcomas and sarcomatoid carcinomas) is a rare subtype with 50 reported cases in the literature and overlapping criteria with undifferentiated carcinoma. We collected and described 15 cases from 10 men and 5 women, with a mean age of 66 years. Symptoms included abdominal pain and gastrointestinal bleeding. Most tumors presented in the rectosigmoid region, with a mean size of 8.2 cm. The sarcomatoid component, on average, represented 58% of the tumors and took many forms, including spindled (10 cases), anaplastic (9 cases), and rhabdoid (3 cases); one case showed osteoid matrix. Tumor budding was usually high, and tumor-infiltrating lymphocytes were usually low. The sarcomatoid component was keratin-positive in 10 cases. One case showed loss of mismatch repair protein expression, and 2 cases showed SMARCA4 loss (1 also with SMARCA2 loss). Molecular testing identified mutations in KRAS (n=1), NRAS (n=2), BRAF (n=2), APC (n=1), and TP53 (n=1) in a few cases. Tumors often presented at advanced stage, with 11 cases pT4, 9 cases with nodal metastases, and 7 cases with distant metastases. Follow-up was available for 10 cases (median: 2 months), with 2 alive without disease, 3 alive with disease, and 5 dead. Our findings roughly corresponded with those in previously reported cases. Colorectal carcinoma with sarcomatoid components is rare and aggressive, with a poor prognosis for many patients. We suggest that spindled cells, anaplasia, heterologous elements, and/or a component with definable sarcomatous lineage be used to distinguish colorectal carcinoma with sarcomatoid components from undifferentiated carcinoma.

Association between tissue human neutrophil peptide 1-3 levels and cardiovascular phenotype: a prospective, longitudinal cohort study.

OBJECTIVE: Inflammation is associated with atherogenesis. Although a higher neutrophil count is associated with the plaque burden, the role of neutrophil activation is unclear. Human neutrophil peptides 1-3 (HNP1-3) are a risk factor for atherogenesis in bench models and are elevated in human atheromas. This study aimed to examine the association between skin HNP1-3 deposition and the severity of coronary artery disease (CAD), including long-term outcomes. METHODS: HNP1-3 levels were immunohistochemically quantified in skin biopsies, which were prospectively taken from 599 consecutive patients before clinically indicated coronary angiography. Established cardiovascular risk factors and blood markers for atheroinflammation were obtained. CAD severity and the incidence of repeat revascularization and mortality at 48 months of follow-up were assessed in relation to HNP1-3 levels. RESULTS: The risk of CAD was independently associated with age and HNP1-3 in the entire cohort (F = 0.71 and F = 7.4, respectively). Additionally, HNP1-3 levels were significantly associated with myocardial necrosis (R = 0.26). At the follow-up, high HNP1-3 levels negatively affected mortality (19.54%) and recurrent revascularization (8.05%). CONCLUSION: HNP1-3 tissue deposition is positively associated with the severity of CAD, myonecrosis, and long-term sequelae. HNP1-3 levels may be suppressed using colchicine.

Rapid intraoperative diagnosis of gynecological cancer by ATR-FTIR spectroscopy of fresh tissue biopsy.

A rapid and reliable intraoperative diagnostic technique to support clinical decisions was developed using Fourier-transform infrared (FTIR) spectroscopy. Twenty-six fresh tissue samples were collected intraoperatively from patients undergoing gynecological surgeries. Frozen section (FS) histopathology aimed to discriminate between malignant and benign tumors was performed, and attenuated total reflection (ATR) FTIR spectra were collected from these samples. Digital dehydration and principal component analysis and linear discriminant analysis (PCA-LDA) models were developed to classify samples into malignant and benign groups. Two validation schemes were employed: k-fold and "leave one out." FTIR absorption spectrum of a fresh tissue sample was obtained in less than 5 minutes. The fingerprint spectral region of malignant tumors was consistently different from that of benign tumors. The PCA-LDA discrimination model correctly classified the samples into malignant and benign groups with accuracies of 96% and 93% for the k-fold and "leave one out" validation schemes, respectively. We showed that a simple tissue preparation followed by ATR-FTIR spectroscopy provides accurate means for very rapid tumor classification into malignant and benign gynecological tumors. With further development, the proposed method has high potential to be used as an adjunct to the intraoperative FS histopathology technique.

Lobular Carcinoma of the Breast Metastatic to the Spleen and Accessory Spleen: Report of a Case.

Despite the fact that accessory spleen (also known as supernumerary spleen, splenunculus, or splenule) can be found in 10-30% of patients undergoing autopsies, metastatic disease occurring in this organ has been barely reported. A case of lobular breast carcinoma metastatic to the spleen and accessory spleen found incidentally at therapeutic splenectomy for severe anemia and thrombocytopenia is described. On microscopic examination both organs revealed severe fibrocongestive changes and extramedullary hematopoiesis with no obvious carcinomatous involvement. Cytokeratin 7, estrogen receptors, and GATA3 immunohistochemistry disclosed the presence of numerous metastatic breast carcinoma cells infiltrating the splenic parenchyma. This case demonstrates that metastatic carcinoma can be encountered, although rarely, in accessory spleens and that cytokeratin stain should be performed in sections of spleens and/or accessory spleens excised from cancer patients in which the presence of malignant epithelial cells is not recognized on routine sections.

CD10: a valuable tool for the light microscopic diagnosis of microvillous inclusion disease (familial microvillous atrophy).

Microvillous inclusion disease (MID) is a specific disorder of the intestinal brush border that leads to intractable secretory diarrhea in infants. At present, electron microscopic analysis is required for its definitive diagnosis. However, this technique is not always available or feasible, and the diagnostic microvillous inclusions may not be evident in all specimens. Accordingly, the availability of a panel of histochemical and immunohistochemical stains displaying a specific staining pattern for MID will allow pathologists to reach a definitive diagnosis of this disorder without recourse to electron microscopy. CD10 is a membrane-associated neutral peptidase, shown to have a linear brush-border staining pattern in normal small intestine. We studied the staining pattern of CD10 in small intestinal biopsies from six patients with MID and in 24 control cases (10 normal small intestine, 10 celiac disease, two autoimmune enteropathy, and two allergic enteropathy). All MID cases revealed prominent cytoplasmic CD10 immunoreactivity in surface enterocytes. In contrast, all control cases showed linear brush-border staining. Similar results were obtained with periodic acid-Schiff, polyclonal carcinoembryonic antigen, and alkaline phosphatase, three stains known to show cytoplasmic staining of surface enterocytes in MID. In conclusion, CD10 is a valuable tool for the diagnosis of MID. It may be used as part of a panel that includes other stains with a distinctive staining pattern in MID such as periodic acid-Schiff, polyclonal carcinoembryonic antigen, and alkaline phosphatase. We suggest that the definitive diagnosis of MID can be reached when small bowel biopsies from infants with intractable diarrhea display cytoplasmic staining of surface enterocytes with the above-mentioned stains.

The histiocytic marker PG-M1 is helpful in differentiating histiocytes and histiocytic tumors from melanomas.

Previous studies have shown that immunohistochemical stains for histiocytes are immunoreactive for melanomas. Accordingly, their value in differentiating histiocytes and histiocytic lesions from melanomas was questioned. PG-M1, the most specific histiocytic marker, was not evaluated in these studies. Our aims were to assess the reactivity of PG-M1 with a series of primary cutaneous and metastatic melanomas and to establish the potential usefulness of this antibody in the differentiation between histiocytes and histiocytic tumors and melanomas. PG-M1 staining was performed in 50 primary cutaneous and metastatic melanomas. For comparison, additional sections were stained with KP-1 and lysozyme (commonly used as histiocytic markers) and with S-100 and HMB-45 (commonly used as melanoma markers). The intensity (1+, 2+) and extent (1+ to 4+) were recorded semiquantitatively. PG-M1 stained weakly (1+) and focally (2+) only four cases of melanoma (8%). In contrast, histiocytes were strongly reactive for PG-M1 in all cases, being readily differentiated from melanoma cells including the positive cases. KP-1 stained melanoma cells in 44 cases (88%), lysozyme in 11 cases (22%), S-100 in 50 cases (100%), and HMB-45 in 48 cases (96%). No changes were found after restaining of selected KP-1 and lysozyme positive melanomas using an endogenous avidin/biotin blocking kit. PG-M1 is helpful in discriminating histiocytes and histiocytic lesions from melanoma cells. We recommend its inclusion in any antibody panel put together to distinguish between them.

Prevalence of HIV with conjunctival squamous cell neoplasia in an African provincial hospital.

PURPOSE: To evaluate the prevalence of HIV seropositivity among patients with malignant conjunctival squamous cell carcinoma (SCC) and carcinoma in situ (CIS) and to reassess the potential linkage, albeit well documented, between ocular surface epithelial dysplasia (OSED) and HIV infection. PATIENTS AND METHODS: A case-control design study was conducted in an African provincial hospital. Twenty-three African black patients underwent excisional biopsy of conjunctival malignant lesions. In 18 of these patients, ELISA for HIV antibodies was performed prior to the excisional biopsy. RESULTS: Pathological evaluation revealed SCC in 12 (52%) patients, CIS in six (26%) patients, and Kaposi sarcoma (KS) in five (22%) patients. Eighteen patients (78.3%) agreed to take a serological HIV test, and among these, seropositivity for HIV was significantly (p < 0.01) higher (92.3%, 12 of 13) in the SCC/CIS subgroup than in a control group with benign conjunctival lesions (28.5%, two of seven). The most common (91.7%) clinical finding in the SCC/CIS/HIV group (12 patients) was corneal overriding. Conjunctival malignancy was the first presenting sign for AIDS in 50% of our patients. CONCLUSIONS: A significantly high rate of HIV seropositivity was found in a group of African black patients with conjunctival SCC/CIS compared with a control group with benign conjunctival lesions. The direct correlation between HIV infection and SCC/CIS was reconfirmed in a case-control study. Therefore, an HIV test should probably be performed in cases of conjunctival SCC/CIS or dysplasia, especially among patients in high-risk populations.

Small intestinal amyloidosis: a rare cause of diverticular disease.

Systemic amyloidosis frequently involves the small intestine. However, its association with diverticular disease has been seldom reported to date. To draw attention to this rare but potentially harmful association, we herein present an additional case of small bowel diverticular disease associated with amyloidosis.

Metastatic carcinoma occurring in a gastric hyperplastic polyp mimicking primary gastric cancer: the first reported case.

Hyperplastic polyps of the stomach are regarded as benign. However, in rare cases they may contain incipient primary carcinomas. To our knowledge, breast carcinoma metastatic to a gastric hyperplastic polyp has not yet been reported. We describe the case of a 69-year-old woman to whom a gastric polyp was endoscopically excised. The patient had previously undergone a right mastectomy for mixed, invasive ductal and lobular carcinoma 5 years earlier. Histological sections from the gastric lesion showed typical features of hyperplastic polyp with foci of poorly differentiated adenocarcinoma including signet ring cells infiltrating the lamina propria. The histologic findings were consistent with a primary gastric cancer. However, the carcinoma cells were immunopositive for estrogen and progesterone receptors and GATA3 and negative for CDX2, Hep Par 1, and MUC5AC. E-cadherin showed membranous reactivity in some of the carcinoma cells while in others it was negative. Accordingly, metastatic mixed, lobular and ductal breast carcinoma was diagnosed. We conclude that metastatic adenocarcinoma mimicking primary gastric cancer can be rarely encountered in hyperplastic gastric polyps.

Angiolipofibroma of the cecum: a rare type of submucosal polyp.

Mesenchymal type tumors originated in the submucosa represent a small percentage of colorectal polyps. This is particularly true for polyps composed of more than one mesenchymal tissue type. We herein present the pathological features of an unusual polypoid proliferation of mature fatty, fibrous, and vascular tissues including vessels of diverse nature and size. The histological findings support a hamartomatous rather than a true neoplastic origin for this rare lesion.

Colonic perineuriomas with and without crypt serration: a comparative study.

Colorectal perineuriomas are characterized by a mucosal proliferation of benign stromal cells expressing perineurial markers leading to separation and/or disorganization of the crypts that frequently display a serrated/hyperplastic architecture. Previous studies demonstrated a high prevalence of a BRAF p.V600E mutation in perineuriomas with serrated crypts and suggested that perineuriomas without crypt serration may represent an unrelated, different type of polyp. Yet, these molecular analyses included only 2 cases of perineuriomas without crypt serration. In fact, no previous studies can be found in the literature that have separately analyzed serrated and nonserrated perineuriomas and made a comparison between them. We retrospectively evaluated the clinical, histologic, immunohistochemical, and molecular features of 15 perineuriomas without and 45 with crypt serration (NSPs and SPs, respectively). No significant differences were found between the groups with regard to sex, age, location, and size. Histologically, the perineurial proliferation in SPs and NSPs demonstrated similar features with fascicles or bundles of bland, plump spindle cells surrounding and separating the crypts. All lesions showed expression with at least 2 of 4 perineurial cell markers (epithelial membrane antigen, claudin-1, GLUT-1, and collagen type IV). Molecular analysis performed in 20 cases (8 SPs and 12 NSPs) identified BRAF mutation of codon 600 in 5 (62%) SPs including 3 with p.V600E (c.1799T>A) and 2 with p.V600R (c.GT1798_99GT>AG). In contrast, no case of NSPs harbored BRAF mutations (p value 0.004). Our findings confirm that BRAF mutations originate in the serrated epithelium of SPs and demonstrate that SPs and NSPs have similar clinical and endoscopic characteristics and similar stroma, suggesting that they might represent 2 variants of a single lesion.

Fibroblastic polyp of the colon and colonic perineurioma: 2 names for a single entity?

Fibroblastic polyps of the colon and intestinal perineuriomas are unusual mucosal lesions with identical clinical and histologic features, and apparent different immunohistochemical and ultrastructural characteristics. However, immunohistochemical distinction was solely based on the results obtained with epithelial membrane antigen (EMA), an antibody whose reactivity on perineuriomas is difficult to demonstrate. Likewise, accurate ultrastructural diagnosis may be flawed by sampling error, preservation artifacts, or paucity of specific diagnostic features. In a recent short communication, it was suggested that both lesions may represent the same entity. To further evaluate this hypothesis, 28 colorectal polyps with clinical and histologic features of colonic fibroblastic polyps/perineuriomas (including 10 cases previously reported as fibroblastic polyps) were stained immunohistochemically for 4 markers of perineurial differentiation, that is, claudin-1, GLUT-1, collagen type IV, and EMA (the latter performed using an extended protocol for antigen retrieval and a kit for signal amplification). In addition, electron microscopy was performed in 4 cases. EMA and claudin-1 stained 26 of 28 (93%) polyps whereas GLUT-1 and collagen type IV were expressed in all of them. EMA reactivity was mostly focal and weak whereas the other markers displayed a diffuse and strong signal. Ultrastructural examination revealed elongated cells with features of perineurial differentiation including long, slender cytoplasmic processes with pinocytotic vesicles and an external lamina. Our findings support the hypothesis that fibroblastic polyps and perineuriomas of the colon represent the same entity. We suggest reclassifying fibroblastic polyps reactive to perineurial markers as perineuriomas. To reach an accurate diagnosis, we recommend employing at least 2 markers of perineurial differentiation, and performing EMA immunostaining with high antibody concentration, prolonged incubation time, and/or extended protocol for antigen retrieval.

Utility of MIB-1 (Ki-67) in evaluating diminutive colorectal polyps with cautery artifact.

CONTEXT: Accurate interpretation of colorectal polyp histology is essential in the decision-making process during treatment and surveillance following polypectomies. However, interpretation of diminutive colorectal polyps removed by thermal electrocoagulation (hot biopsy technique) is often problematic as a result of cautery artifact. OBJECTIVE: To evaluated the usefulness of the proliferation marker MIB-1 (Ki-67) as an aid in the differential diagnosis of diminutive colorectal polyps with cautery artifact, as adenomatous and nonadenomatous polyps display different patterns of epithelial proliferation. DESIGN: Seventy-five diminutive colorectal polyps with extensive cautery artifact displaying at least the upper portions of 3 adjacent crypts with the corresponding surface epithelium were evaluated and immunolabeled with MIB-1. They included 25 cases in which a definitive or presumptive diagnosis could not be reached (indeterminate polyps), 25 cases diagnosed as compatible with adenomatous polyp, and 25 cases diagnosed as compatible with nonadenomatous polyp. RESULTS: MIB-1 immunoreactivity was well preserved in the cauterized areas. Among indeterminate polyps, MIB-1 stained upper crypts and surface epithelium in 14 cases (adenomatous polyp staining pattern) and revealed minimal or absent staining in these areas in 11 cases (nonadenomatous polyp staining pattern). All cases diagnosed as compatible with adenomatous polyp displayed the adenomatous polyp staining pattern. In contrast, all cases diagnosed as compatible with nonadenomatous polyp revealed the nonadenomatous polyp staining pattern. CONCLUSIONS: Immunoreactivity for MIB-1 may be used as a beneficial adjunctive test to help diagnose diminutive colorectal polyps with extensive cautery artifact.

Expression of the intestinal marker Cdx2 in secondary adenocarcinomas of the colorectum.

CONTEXT: Secondary adenocarcinomas of the large bowel can closely mimic primary tumors. The differentiation of secondary from primary adenocarcinomas of the colorectum, however, is important because their clinical management and prognosis are different. Immunostaining with the nuclear transcription factor Cdx2, expressed in normal intestinal epithelia and colorectal adenocarcinomas, could be of potential diagnostic use. OBJECTIVE: To investigate the diagnostic value of Cdx2 immunoexpression in distinguishing primary from common forms of secondary colorectal adenocarcinomas. DESIGN: Cdx2 immunoexpression was analyzed in 20 primary colorectal adenocarcinomas and in 34 secondary colorectal adenocarcinomas and their corresponding primary tumors. All secondary tumors were diagnosed through endoscopic biopsies and included 8 cases of ovarian (4 serous, 2 mucinous, and 2 endometrioid), 6 of mammary (4 lobular and 2 ductal), 4 of gastric (2 intestinal and 2 diffuse), 4 of pulmonary, 4 of pancreatic (ductal), 3 of prostatic, 3 of colorectal, and 2 of endometrial origin. RESULTS: Cdx2 was expressed in normal colorectal epithelium, in primary colorectal adenocarcinomas (20/20 cases), in secondary adenocarcinomas of colorectal (3/3) and gastric (3/4) origin, and in metastatic ovarian mucinous adenocarcinomas (2/2). In contrast, no Cdx2 immunoreactivity was observed in secondary colorectal tumors of ovarian (serous and endometrioid), mammary, pancreatic, pulmonary, prostatic, and endometrial origin. CONCLUSION: Cdx2 immunostaining may be useful in discriminating primary colorectal carcinomas from frequent types of secondary colorectal adenocarcinomas of nongastrointestinal origin. We suggest including Cdx2 in any antibody panel put together to distinguish between primary and secondary epithelial colorectal malignancies.

CD10 is helpful in detecting occult or inconspicuous endometrial stromal cells in cases of presumptive endometriosis.

BACKGROUND: Previous studies have shown that CD10 is a marker for normal, ectopic, and neoplastic endometrial stromal cells. However, its value in confirming a diagnosis of presumptive endometriosis has not been extensively studied. OBJECTIVE: To assess the reactivity of CD10 in a series of cases of presumptive endometriosis and to establish the potential usefulness of this antibody in confirming the diagnosis. DESIGN: We studied hematoxylin-eosin sections and immunoreactivity of CD10 in 20 cases diagnosed as "suspicious for," "suggestive of," or "compatible with" endometriosis as well as in 12 cases of lesions that may be confused with endometriosis (3 endosalpingioses, 3 mesothelial hyperplasias, 3 ovarian follicular cysts, and 3 hemorrhagic corpora lutea). RESULTS: Routine sections from cases of presumptive endometriosis showed glands lacking a distinct cuff of endometrial stromal cells because of atrophy or because of changes secondary to hemorrhage, inflammation, fibrosis, and/or cystic dilatation. In a few cases, the distinction between endometrial and ovarian stroma could not be assessed with certainty. CD10 immunostaining confirmed the diagnosis in 17 (85%) of the cases, as it strongly stained endometrial stromal cells that were not apparent on hematoxylin-eosin sections. All sections from lesions that may simulate endometriosis were CD10-. CONCLUSION: CD10 is helpful in detecting occult or inconspicuous ectopic endometrial stromal cells and in distinguishing endometriosis from its potential mimickers. We recommend its use to confirm or exclude the presence of endometrial stromal cells in cases of presumptive endometriosis and in lesions that may be mistaken for this entity.

The value of Cdx2 immunostaining in differentiating primary ovarian carcinomas from colonic carcinomas metastatic to the ovaries.

Histologic differentiation of primary ovarian carcinoma from colonic carcinoma metastatic to the ovary may be difficult. Cytokeratin 7 (CK7) and cytokeratin 20 (CK20) immunostaining is usually used, but these markers lack specificity for ovarian and intestinal epithelium, and overlapping results have been reported. Cdx2 is a transcription factor whose expression in normal tissues is limited to the intestinal epithelium. It is also expressed in the vast majority of colonic carcinomas and in a sizeable proportion of cases of gastric, pancreatobiliary, and ovarian mucinous carcinomas. We evaluated Cdx2, CK7, and CK20 expression in 50 ovarian carcinomas (15 serous, 20 mucinous, and 15 endometrioid), 15 colonic carcinomas metastatic to the ovaries, and 20 primary colonic carcinomas. The extent (1-25%/1+, 26-75%/2+, >75%/3+) and intensity (weak/1+, strong/2+) of staining were recorded semiquantitatively. All primary and metastatic colonic carcinomas had diffuse (3+) strong Cdx2 reactivity. All serous and endometrioid tumors were Cdx2 negative, whereas mucinous carcinomas had 1+ or 2+ immunoreactivity. All ovarian carcinomas had strong diffuse CK7 staining, whereas all colonic carcinomas were negative for CK7. CK20 stained diffusely and strongly all primary and metastatic colonic carcinomas and was 1+ or 2+ in all mucinous carcinomas, in 67% of serous carcinomas, and in 33% of endometrioid carcinomas. In conclusion, 1) Cdx2 is a highly sensitive (100%) marker for colonic carcinoma metastatic to the ovary; 2) Cdx2 is more specific than CK20 as it is not expressed by serous and endometrioid carcinomas; and 3) a limited panel of Cdx2 and CK7 helps in distinguishing colonic carcinomas metastatic to the ovaries (Cdx2+/CK7-) from primary ovarian serous (Cdx2-/CK7+), endometrioid (Cdx2-/CK7+), and mucinous (Cdx2+/CK7+) carcinomas.

Expression of the intestinal marker Cdx2 in the columnar-lined esophagus with and without intestinal (Barrett's) metaplasia.

Barrett's esophagus is diagnosed when goblet cells are found in the lower esophageal mucosa. However, the distribution of these cells is patchy and they may not represent the earliest marker of intestinal metaplasia. Cdx2 is a transcription factor whose expression in normal tissues is restricted to intestinal-type epithelium. Its distribution in the columnar-lined esophagus with and without intestinal metaplasia has been seldom studied. We evaluated Cdx2 expression in lower esophageal biopsies from 90 patients with endoscopic diagnosis of short segment Barrett's esophagus, including 45 consecutive cases showing intestinal metaplasia (goblet cells present in hematoxylin eosin and/or Alcian blue stains) and 45 consecutive cases without goblet cells. 25 samples of cardiac-type mucosa without intestinal metaplasia biopsied from the stomach served as controls. All cases with intestinal metaplasia revealed Cdx2 reactivity in goblet cells and adjacent nongoblet columnar cells. Dysplastic foci, seen in five cases from this group, were Cdx2 positive. In the group without goblet cells, Cdx2 was focally expressed by columnar cells in 17 (38%) cases. All control cases were Cdx2 negative. Strips of Alcian blue-positive nongoblet columnar cells ('columnar blues') were observed in 11 (24%) of the cases without intestinal metaplasia. All these foci were Cdx2 negative. In conclusion, Cdx2 is a highly sensitive marker for Barrett's esophagus. It is also expressed in a significant minority of cases of columnar-lined esophagus without goblet cells, suggesting that it may detect intestinal phenotypic modifications in the absence of goblet cells. Accordingly, Cdx2 immunostaining could help identify patients with Barrett's metaplasia in cases where no goblet cells are visible in biopsies from the columnar-lined esophagus. Finally, lack of Cdx2 expression in the 'columnar blues' suggests that these cells are not diagnostic of intestinal metaplasia.