Is routine appendectomy at the time of primary surgery for mucinous ovarian neoplasms beneficial?

UNLABELLED: The question whether the appendix should be removed at the time of surgery for apparent early-stage ovarian cancer is controversial. Removal of the appendix in the setting of mucinous histologic type is primarily driven by the existing challenge to distinguish between primary ovarian mucinous neoplasm and metastatic appendiceal carcinoma to the ovary. OBJECTIVES: To evaluate the value of an appendectomy at the time of surgery for ovarian mucinous borderline tumors or carcinoma. METHODS: A retrospective single institute-based study was conducted. We identified patients who were operated on by a gynecologic oncologist for an abnormal pelvic mass, which was diagnosed as mucinous adenocarcinoma or mucinous borderline tumor between January 2000 and December 2010. Cases were included in the study if an appendectomy was performed at the time of initial surgery. RESULTS: Seventy-seven cases meeting the inclusion criteria were identified. The ovarian mass of 11 patients (14%) was diagnosed as metastatic appendiceal carcinoma involving the ovary. Evidence of metastatic disease, abnormal-looking appendix, or pseudomyxoma peritonei, were identified at the time of surgery for all of these cases. The condition of 30 patients (39%) and 36 patients (47%) were diagnosed as mucinous borderline ovarian tumor and invasive or microinvasive mucinous ovarian carcinoma, respectively. Evidence of metastasis from the ovary to the appendix was not identified in any of the cases. CONCLUSIONS: Our data suggest that in cases of apparent early-stage mucinous ovarian borderline tumors and cancer, adding an appendectomy at the time of surgery is not warranted in the absence of a grossly abnormal appendix or evidence of metastatic disease.

Significance of loss of heterozygosity in predicting axillary lymph node metastasis of invasive ductal carcinoma of the breast.

Invasive ductal carcinoma (IDC) of breast metastatic to axillary lymph node (ALN) is a critical factor in determining stage and is a strong predictor of disease prognosis and survival. We studied ALN metastasis using a combined histopathologic/molecular approach to gain insights into the pathobiology implications. Fourteen patients with IDC with positive ALN and 19 with negative ALN were retrieved. Analysis of 17 polymorphic microsatellite repeat markers targeting 1p34-36, 3p24-26, 5q23, 9p21, 10q23, 17p13, 17q12, 17q21, 21q22, and 22q13 was carried out in DNA isolated from primary tumors and metastatic tumors. ALN metastasis correlated with fractional mutation rate of primary and ALN metastatic tumors, primary tumor size, and nuclear grade, and did not correlate with expression of estrogen receptor, progesterone receptor, and Her2/neu. Loss of heterozygosity (LOH) detected at 1p34-36, 3p24-26, 9p21, 10q23, 17p13, 17q12, 21q22, and 22q13 may play an important role in the development and aggressiveness of IDC, and LOHs at 1p34-36, 17p13, and 22q13 may play an important role in metastasis. None of the LOHs were shared by all the tumors, suggesting that IDC develops through various pathways that have unique and personalized patterns of mutational changes, although they share similar morphology. Detection of LOH in IDC is not only useful in studying oncogenesis, but also predicting aggressiveness and ALN metastasis.

The diagnostic utility of CK5/6 and p63 in fine-needle aspiration of the breast lesions diagnosed as proliferative fibrocystic lesion.

Fine-needle aspiration (FNA) biopsy (FNAB) in the preoperative assessment of breast lesions has shown diagnostic limitations with false-positive and false-negative diagnoses. We investigated the diagnostic value of cytokeratin 5/6 (CK5/6) and p63 in a series of breast FNABs, diagnosed as proliferative breast lesions with or without atypia, to see whether these ancillary studies enhance the ability to make an accurate diagnosis by FNAB. Sixty-four breast FNABs were retrieved between January 2000 and December 2005 and included in the study as follows: 29/64 (45%) cases as proliferative with atypia and 35/64 (55%) without atypia. We also included 10 cases of fibroadenoma. All cases had histological follow-up available for correlation. Immunostaining for CK5/6 and p63 was performed on the cell block material in all cases. The percentage of staining cells in the specimen was graded as 0 (0-10%), 1 (11-25%), 2 (26-50%), and 3 (>50%). There were 9/29 (31%) cases in the atypical group that were found to be malignant on resection, compared with 6/35 (17%) in the cases without atypia. In histologically proven malignant cases, CK5/6 was negative in 11/15 (73%) or showed 1+ stain in 2/15 (13%) cases. In benign breast lesions, CK5/6 stained more than 25% of cell proliferation in 44/49 (90%). p63 showed characteristic staining for single naked bipolar nuclei in the background of the specimen (not appreciated by CK5/6) in all fibroadenoma cases. In conclusion, CK5/6 may enhance the ability to differentiate between benign and malignant epithelial proliferations in breast FNABs. In fibroepithelial lesions, p63 may be more useful than CK5/6.

Fine-needle aspiration biopsy of breast adenomyoepithelioma: a potential false positive pitfall and presence of intranuclear cytoplasmic inclusions.

Cytologic diagnosis of adenomyoepithelioma can be very challenging. We report fine needle aspiration cytology (FNAC) findings of a benign adenomyoepithelioma. The cytologic features are characterized by hypercellularity and the presence of numerous atypical dispersed cells with epithelioid morphology and intact cytoplasm. The nuclei showed stippled chromatin, irregular nuclear membrane, and prominent eosinophilic nucleoli. No necrosis or mitoses were seen. The presence of naked nuclei, and extensive intranuclear cytoplasmic inclusions were identified and raised the possibility of adenomyoepithelioma. Immunohistochemically, the atypical cells showed strong positivity for myosin heavy chain, p63, and CK5/6, while the epithelial cells reacted with estrogen receptors. This immunophenotypic pattern supports the myoepithelial origin of the atypical cell proliferation and favors the diagnosis of benign adenomyoepithelioma. However, biopsy was recommended to exclude malignancy. Histologically, the tumor showed prominent myoepithelial cells with significant atypia, intranuclear cytoplasmic inclusions, and dense cytoplasm. No evidence of malignancy was identified. In conclusion, we report a case of adenomyoepithelioma with a significant cytological atypia that may result in confusion with malignant breast tumors. The presence of intranuclear cytoplasmic inclusions, naked nuclei, and expression of myoepithelial markers should provide clues to the right diagnosis and benign nature of this lesion. Cytopathologists should be familiarized with this entity to avoid a misdiagnosis of carcinoma.

P16INK4a expression in undifferentiated carcinoma of the uterus does not exclude its endometrial origin.

Undifferentiated carcinoma of the endometrium is a rare neoplasm, which, when involving the cervix, raises a question about its origin. Diffuse p16 positivity of uterine cancers is usually interpreted as a surrogate marker for high-risk human papilloma virus and favors cervical origin. In this study, we investigated the expression of cytokeratin 7 (CK7), monoclonal carcinoembryonic antigen (mCEA), estrogen receptor (ER), vimentin, and p16 in 28 cases of undifferentiated endometrial carcinoma, 20 high-grade endometrioid adenocarcinomas, and 50 cervical adenocarcinomas. Staining was considered positive when it was cytoplasmic for CK7, mCEA, and vimentin, nuclear for ER, and both nuclear and cytoplasmic for p16. Percentages of cells staining were recorded as follows: negative (0%-5%), 1+ (6%-25%), 2+ (26%-50%), 3+ (51%-75%), and 4+ (>75%). P16 was considered positive if it stained more than 75% of the tumor cells. Diffuse/strongly positive staining for p16 was seen in 40/50 (80%) cases of cervical adenocarcinoma and 14/28 (50%) cases of undifferentiated endometrial carcinoma. In high-grade endometrioid adenocarcinoma, staining was mainly patchy. CK7, mCEA, ER, progesterone receptor, and vimentin staining in undifferentiated endometrial carcinoma was as follows: 10/28 (36%), 4/28 (14%), 21/28 (75%), 23/28 (82%), and 26/28 (93%), respectively; for high-grade endometrioid carcinoma: 20/20 (100%), 1/20 (5%), 17/20 (85%), 18/20 (90%), and 19/20 (95%); for endocervical adenocarcinoma: 50/50 (100%), 45/50 (90%), 9/50 (18%), 8/50 (16%), and 6/50 (12%), respectively. Our data indicate that p16 may play a role in the tumorigenesis of a subset of undifferentiated endometrial carcinoma. In the setting of p16 positivity, undifferentiated endometrial carcinomas are more likely to be ER, progesterone receptor, and vimentin positive and mCEA negative when compared with endocervical adenocarcinomas. Distinction between undifferentiated endometrial carcinoma and endocervical adenocarcinoma, both of which can share diffuse p16 expression, should rely on detection of human papilloma virus in the latter.

Immunohistochemical characterization of primary and recurrent adult granulosa cell tumors.

Adult granulosa cell tumors are usually diagnosed at an early stage. However, most patients with advanced or recurrent disease will die of the disease due to limited treatment options. Data on the immunohistochemical characteristics of recurrent granulosa cell tumors are limited. The aim of this study was to compare the immunohistochemical profile of primary and recurrent adult granulosa cell tumors. Special emphasis is given to epidermal growth factor receptor expression because it represents a potential marker for targeted therapy with monoclonal antibodies.Inhouse granulosa cell tumor cases accessioned between 1999 and 2008 were retrieved and reviewed according to the WHO classification. Cases were studied by immunohistochemistry using a panel of 11 antibodies. Immunostaining was semiquantitatively recorded.We have studied 20 cases of primary and 20 cases of recurrent adult granulosa cell tumors from 31 patients. Immunohistochemistry showed that primary tumors were positive for inhibin in 100%, calretinin 100%, CD56 90%, CD99 40%, D2-40 35% and low molecular weight keratin 30%. Recurrences were positive for inhibin 90%, calretinin 85%, CD56 95%, CD99 65%, D2-40 55% and low molecular weight keratin 10%. Recurrences were positive for inhibin 90%, calretinin 85%, CD56 95%, CD99 65%, D2-40 55%, and low molecular weight keratin 10%. All primary and recurrent tumors were negative for melan-A, CD10, and epithelial membrane antigen. Epidermal growth factor receptor was positive in 65% of primary tumors and 85% of recurrences. Ki67 index was higher in recurrence specimens. The immunoprofile of primary and recurrent adult granulosa cell tumors is highly concordant. Similar to primary tumors, almost all recurrent cases exhibited evidence of sex cord lineage. The lack of specific markers emphasizes the need for evaluation using a panel of antibodies. Special attention should be paid when low molecular-weight keratin is used as part of a panel differentiating granulosa cell tumors from carcinomas, as a significant proportion of the former are positive. Although targeted therapies directed against epidermal growth factor receptor have not been tested yet in the setting of advanced or recurrent granulosa cell tumors, the high level of epidermal growth factor receptor expression is important as we step to an era of advanced biolabeled imaging techniques.

CDX2 as a marker for intestinal differentiation: Its utility and limitations.

CDX2 is a nuclear homeobox transcription factor that belongs to the caudal-related family of CDX homeobox genes. The gene encoding CDX2 is a nonclustered hexapeptide located on chromosome 13q12-13. Homeobox genes play an essential role in the control of normal embryonic development. CDX2 is crucial for axial patterning of the alimentary tract during embryonic development and is involved in the processes of intestinal cell proliferation, differentiation, adhesion, and apoptosis. It is considered specific for enterocytes and has been used for the diagnosis of primary and metastatic colorectal adenocarcinoma. CDX2 expression has been reported to be organ specific and is normally expressed throughout embryonic and postnatal life within the nuclei of epithelial cells of the alimentary tract from the proximal duodenum to the distal rectum. In this review, the authors elaborate on the diagnostic utility of CDX2 in gastrointestinal tumors and other neoplasms with intestinal differentiation. Limitations with its use as the sole predictor of a gastrointestinal origin of metastatic carcinomas are also discussed.

Idiopathic hypertrophic pyloric stenosis in an adult, a potential mimic of gastric carcinoma.

Primary or idiopathic hypertrophy of the pyloric muscle (IHPM) is a rare entity with uncertain pathogenesis which both clinically and pathologically mimics gastric cancer. We present a rare late-occurring case of IHPM in a 71-year-old Caucasian man with no apparent predisposing factor. Imaging studies demonstrated gastric distension with air fluid levels and no evidence of extrinsic compression. At upper endoscopy, massive gastric distension and no evidence of any ulcer or other mucosal defects were observed. Microscopically, marked hypertrophy of muscularis mucosa with smooth muscle cells arranged in whorls and fascicles was present which gradually transitioned to normal areas. The muscle fibers stained with smooth muscle actin and trichrome stain highlighted fibrosis between the muscle fibers. Although uncommon, IHPM can clinically and histologically mimic other proliferations in the gastric wall, such as gastrointestinal stromal tumor or a spindle cell neoplasm. The recent advances in understanding the pathogenesis of IHPM are discussed.

Ovarian adenosarcoma arising from benign cystadenoma and associated intraoperative consultation pitfalls.

An unusual case of ovarian adenosarcoma arising from a smooth-walled serous cystadenoma is described. The ovary was replaced by a multiloculated, fluid-filled cyst without any solid or papillary areas. The malignant component was underdiagnosed during frozen section examination as benign cystadenoma because of the deceptively benign gross appearance of the tumor. On the permanent sections, a phyllodes-like pattern of stromal proliferation and periglandular condensation of atypical stromal cells with a mitotic count of 3 per 10 high-power fields was more apparent and led to the diagnosis of adenosarcoma. The malignant component could not be distinguished from the benign component using immunohistochemical analysis. To our knowledge, this is the first reported case of an adenosarcoma arising from a grossly benign cystadenoma and the third case in the literature of an adenosarcoma associated with a cystadeno(fibro)ma. This case also shows the challenges in differentiating adenosarcoma from a benign counterpart on both frozen and permanent sections.

Peritumoral lymphatic vessel density as a prognostic parameter in endometrial carcinoma: an immunohistochemical study.

CONTEXT: Lymphatic invasion and nodal metastasis play a major role in the spread and prognosis of endometrial adenocarcinoma (EC). AIMS: In this study, we investigate tumor lymph-angiogenesis, detected by D2-40, as a predictive marker for the risk of lymph node (LN) metastasis and its relation to other prognostic parameters in EC. MATERIALS AND METHODS: Fifty-five cases of EC treated with total hysterectomy and pelvic LN dissection were reviewed. All cases were immunostained for D2-40. Positively stained microvessels (MV) were counted in densely lymphovascular foci (hotspots) at X 400 field (0.17 mm2). STATISTICAL ANALYSIS: Statistical analysis was performing using Chi square "X 2" test. RESULTS: Lymphovascular invasion was detected in 20 / 55 patients by D2-40 and 14 / 55 by routine hematoxylin and eosin (H and E). Peritumoral lymphatic vessel (LV) count was significantly higher than intratumoral LV count (17 + 7 versus 5 + 4 / 0.17 mm 2 , P < 0.01). Peritumoral D2-40 lymphovascular counts correlated significantly with FIGO grade (P < 0.001), lymphovascular invasion (P = 0.001) and LN metastases (P = 0.005). However, it showed non-significant correlation with peritoneal wash positivity (P = 0.830) and stage of the disease (P = 0.341). Intratumoral lymphovascular invasion detected by D2-40 showed significant correlation with LN metastases (P < 0.01). CONCLUSIONS: Our study shows that assessing LVD with D2-40 in the endometrial carcinoma might be a valuable parameter for predicting patients having an increased risk of developing of metastatic disease. In addition, D2-40 increases the frequency of detection of lymphatic invasion relative to routine H and E stain.

Lymphatic vessel density as a prognostic marker in clinical stage I endocervical adenocarcinoma.

There are limited data evaluating the significance of lymphatic vessel density (LVD) as a prognostic marker in cervical adenocarcinoma. In this study, we investigated intratumoral and peritumoral LVD, using the lymphatic marker D2-40, as a prognostic marker in endocervical adenocarcinoma. Surgical specimens from 50 consecutive patients with endocervical adenocarcinoma treated with complete staging surgical procedures were reviewed. Selected tumor blocks were immunostained for D2-40 and CD31. Positively stained microvessels (MVs) were counted in densely vascular/lymphatic foci (hot spots) at 400x field in each specimen (0.17 mm). Results were expressed as the highest MV count identified within any single field. Both intratumoral CD31 MV and peritumoral D2-40 LVD showed significant correlation with depth of invasion (r=0.39, 0.37, respectively), percentage of circumferential involvement (r=0.36, 0.48, respectively), and lymphovascular invasion detected by D2-40 (r=0.45, 0.51, respectively; P<0.01). Only peritumoral D2-40 LVD showed a significant correlation with lymph node metastases (r=0.40; P<0.01), disease-free and overall survivals. Using univariate analysis, peritumoral D2-40 LVD showed significant correlation with lymphovascular invasion detected by D20-40 and lymph node metastases (P<0.05), which was maintained on multivariate analysis. D2-40 detected lymphovascular invasion in 16 of 50 (32%) cases, and showed a significant correlation with depth of invasion, lymph node metastases, involvement of parametrium (r=0.41, 0.38, 0.32, respectively; P<0.01), and disease-free survival. Our study showed that both angiogenesis and lymphangiogenesis play an important role in the progression of endocervical adenocarcinoma, and that peritumoral D2-40 LVD is an independent predictor of lymph node metastasis.

Distribution of basal/myoepithelial markers in benign and malignant bronchioloalveolar proliferations of the lung.

We investigated the staining pattern of commonly used basal cell/myoepithelial markers, such as p63 (a p53-homologous nuclear protein), basal cell-specific cytokeratin antibody (34betaE12, K903), and smooth muscle myosin heavy chain (SMMHC) in benign and malignant bronchioloalveolar proliferations of the lung. We studied 85 lung lesions consisting of 35 bronchioloalveolar carcinoma, 30 well-differentiated adenocarcinoma, and 20 cases of benign lung lesions. In normal lung, p63, K903, and SMMHC decorated the basal cells of large and small airways and occasional cells of terminal bronchioles. In reactive processes, a distinctive staining pattern was present in 19/20 (95%) of the cases characterized by staining of basal cells of the airways and bronchiolar epithelium and squamous metaplastic epithelium for p63 and K903, whereas 12/20 (60%) stained with SMMHC. Respiratory ciliated cells, alveolar epithelial cells, and nonepithelial cells were negative. In bronchioloalveolar carcinoma, a discontinuous peripheral rim of p63-immunoreactive cells was retained surrounding and intermingled with the malignant bronchioloalveolar proliferation in 31/35 (88.5%) cases, SMMHC in 28/35 (80%) cases, and K903 in 20/35 (57%) cases. For adenocarcinoma, a majority of the cases (28/30, 93%) were negative for p63 and K903; however, SMMHC showed artifactual staining in the desmoplastic stroma in 6/30 (20%) cases. Our results highlighted the differential expression of basal cell markers across various bronchioloalveolar lesions. The staining pattern of basal cells in bronchioloalveolar carcinoma supports that these neoplasms may actually be carcinoma in-situ.

Respiratory cytology: differential diagnosis and pitfalls.

Pulmonary cytology can be challenging and has its share of diagnostic pitfalls. Reactive atypia can occasionally be alarming, leading to diagnostic pitfall for a false-positive diagnosis of malignancy, even for experienced cytopathologists (Naryshkin and Young, Diagn Cytopathol 1993;9:89-97). In addition, cytologic preparations can show an absence of architectural clues, leading to diagnostic difficulties. Some conditions can cytologically as well as clinically and radiographically mimic malignancies, making these pitfalls even more frequent (Bedrossian et al., Lab Med 1983;14:86-95). A recent report stated that "no laboratory that aims to make definitive diagnoses in pulmonary cytology can be spared from false-positive results"(Policarpio-Nicolas and Wick, Diagn Cytopathol 2008;36:13-19). A false-positive finding could produce unnecessary treatment and morbidity, whereas false-negative diagnosis could result in delayed diagnosis and treatment. This review analyzes and illustrates cellular changes and benign entities that can mimic malignancy in respiratory cytology as well as neoplasms that could lead to a false-negative diagnosis. In addition, some specific challenging and difficult aspects in classification of pulmonary malignancies will be discussed. Guidelines and clues are presented to avoid such pitfalls.

Detection of HPV-DNA by a PCR-based method in formalin-fixed, paraffin-embedded tissue from rare endocervical carcinoma types.

High-risk human papilloma virus (HPV) seems to play a role in the pathogenesis of cervical squamous neoplasia and adenocarcinomas of the mucinous and endometrioid cell types. Cervical serous, clear cell, and small cell carcinomas differ from the conventional endocervical adenocarcinoma in their clinical characteristics. The data on the role of HPV in their pathogenesis are limited. In this study, we examined the presence of high-risk HPV-DNA in rare types of cervical carcinoma using polymerase chain reaction-based test. In-house cervical serous, clear cell, and small cell carcinoma cases accessioned between 2000 and 2008 were tested for HPV by polymerase chain reaction amplification of DNA extracted from deparaffinized sections using Roche AMPLICOR HPV Amplification Detection and Control Kits. The kit detects all 13 high-risk HPV-DNA genotypes. The positive cut-off point for AMPLICOR HPV Test was A450 = 0.2. We identified 4 serous, 3 clear cell, 1 mixed clear cell and serous, and 5 small cell carcinomas. High-risk HPV-DNA tested positive in 3 out of 4 serous carcinomas, 2 out of 3 cervical clear cell carcinomas, and all 5 cases of small cell carcinoma and the mixed cell type. Our report documents HPV status in a series of archival unusual types of adenocarcinoma of the uterine cervix. It suggests a robust association between high-risk HPV and these rare subtypes. Despite their unique clinical setting and morphologic appearance, the majority of these tumors likely share a common HPV-mediated carcinogenic pathway. Our observation is particularly significant in cervical cancer prevention as we enter the HPV vaccination era.

CDX-2 expression is a common event in primary intestinal-type endocervical adenocarcinoma.

We studied the expression of cytokeratin (CK) 7, CK20, CDX-2, and p16 in 119 cervical adenocarcinomas (65 usual type [50 invasive; 15 in situ], 37 intestinal type [21 invasive; 16 in situ], 10 endometrioid, 5 adenosquamous, and 2 signet-ring carcinomas) in comparison with 55 cases of rectal adenocarcinomas. The percentage of cells staining was considered negative if 0% to 5% stained; more than 5% was considered positive. For p16, staining of more than 50% was considered positive. CK7 was expressed in all cervical cases and in 12 rectal adenocarcinomas (22%). CK20 was expressed in 17 cervical adenocarcinomas (14.3%) and in 48 rectal adenocarcinomas (87%). CK20 immunostaining was diffuse in the majority of rectal tumors but focal in most cervical tumors. CDX-2 was expressed in all cases of rectal adenocarcinoma and in 46 cervical adenocarcinomas (38.7%): usual type, 10 (15%); intestinal type, 31 (84%); endometrioid type, 5 (50%); adenosquamous and signet-ring types, 0 (0%). CDX-2 is a marker for intestinal differentiation irrespective of a rectal or cervical origin. Therefore, it should not be used as the sole basis to confirm the colorectum as the primary origin in metastatic cases.

Significance of periductal lymphatic and blood vascular densities in intraductal carcinoma of the breast.

We investigated the significance of periductal lymphatic and blood vascular densities in intraductal carcinomas (IDC) of the breast. Thirty five cases of pure IDC treated by partial or total mastectomy were reviewed. Seven cases with normal breast tissue and 48 cases of invasive breast carcinoma were included as controls. All cases were immunostained with D2-40 and CD31. Positively stained microvessels were counted in densely vascular/lymphatic foci (hot spots) at 400x (=0.17 mm(2)) in the periductal areas. IDC without comedonecrosis showed a mean periductal D2-40 lymphatic microvessel density (LMD) of 5.8 +/- 5 (range 0-18), and a CD31 microvessel density (MD) of 14 +/- 8.9 (range 1-40). IDC with comedonecrosis showed periductal D2-40 LMD of 8.4 +/- 3.8 (range 4-18), and a CD31 MD of 24.3 +/- 7.6 (range 14-40). There was a significant difference between periductal D2-40 LMD and CD31 MD counts in IDC with and without comedonecrosis. There was a positive correlation of periductal D2-40 LMD and CD31 MD counts with high nuclear grade (r = 0.39 and 0.56) of IDC as well as with the presence of comedonecrosis (r = 0.49 and 0.59). Both D2-40 LMD and CD31 MD did not correlate significantly with tumor size, estrogen status, or progesterone status. As IDC with comedonecrosis and/or high nuclear grade has a worse prognosis than IDC without comedonecrosis and/or with low nuclear grade, it appears that lymphatic and blood vascular density evaluated by D2-40 and CD31, respectively, are independent prognostic indicators for patients with IDC of the breast and may be an indicator of early or unrecognized invasion or "regression."

Postradical vaginal trachelectomy follow-up by isthmic-vaginal smear cytology: a 13-year audit.

Radical trachelectomy is a fertility preserving alternative for early cervical cancer patients. This audit assesses the role of isthmic-vaginal smear in postoperative follow-up. A total of 94 patients were identified generating 913 smears. The final surgical margin was at the lower uterine segment in 37 cases (39.4%) and significantly correlated with the presence of lower uterine segment endometrial cells (LUSEC) in smears (P = 0.035). The most common abnormal diagnoses in the presence of LUSEC were ASC-US and AGUS seen in 14.2% and 11.9% of positive smears, respectively. The most common follow-up pattern was initial positive smears, which converted to negative (45.7% of patients), showing that reactive changes are another potential overcall pitfall. The only 2 central recurrences were successfully diagnosed by smears. This study summarizes our experience, emphasizing the role of isthmic-vaginal smears for early detection of central recurrence and highlighting the role of LUSEC and reactive changes as potential overcall pitfalls.

CDX2, cytokeratins 7 and 20 immunoreactivity in rectal adenocarcinoma.

There are limited data regarding CDX2 expression in rectal carcinoma. The CK20/CK7 immunoprofile of colorectal adenocarcinoma has been described in studies, which have mostly lumped colonic and rectal tumors together. In this study, we investigated the diagnostic utility of immunohistochemical stains for CK7, CK20, and CDX2 in a series of rectal adenocarcinoma. Fifty-five specimens of rectal adenocarcinomas were retrieved and immunostained for CK7 (Dako-M7018), CK20 (NovoCastra NCL-L-CK20), and CDX2 (NovoCastra NCL-CDX2). Thirty cases of pancreatic adenocarcinoma and 15 cholangiocarcinomas were also studied as a comparison group. CK7 was expressed in 12/55 (22%) and CK20 in 48/55 (87%) cases of rectal adenocarcinoma. The CK7-/CK20+ immunophenotype was identified in 36/55 (65%), CK7+/CK20+ in 12/55 (22%), and CK7-/CK20- in 7/55 (13%) rectal adenocarcinoma. CDX2 showed moderate-strong positivity in all cases and was not related to tumor differentiation. Benign rectal mucosa was available in 37 cases and showed the following results: CK7-/CK20+ in 25/37 (67%), CK7+/CK20+ in 8/37 (22%) and CK7-/CK20- in 4/37 (11%) cases. In pancreatic adenocarcinomas and cholangiocarcinomas, 29/45 (64%) were CK7+/CK20+ and 16/45 (36%) were CK7+/CK20-. CDX2 was positive in only 3/45 (7%) of these cases; all were pancreatic adenocarcinomas. In conclusion, CK7 can be expressed in rectal adenocarcinoma, and should not be used as the sole basis for excluding a rectal primary. CDX2 is a sensitive marker for rectal origin of adenocarcinoma. It can be helpful in cases with metastatic rectal carcinoma, especially those with CK7+/CK20+ or CK20-/CK7- immunophenotype. In this study, CDX2 expression was not influenced by the grade (differentiation) of rectal adenocarcinoma.

Lymphatic vessel density as prognostic marker in esophageal adenocarcinoma.

We studied tumor lymphatic vascular density (LVD) as a predictive marker for the risk of lymph node (LN) metastasis and its relationship to other prognostic parameters and survival in 75 patients with esophageal adenocarcinoma. Samples were immunostained for D2-40, CD31, and vascular endothelial growth factor (VEGF). Microvessels were counted in densely vascular/lymphatic foci (hot spots) at x400 field (0.17 mm2). Intensity of staining for VEGF was scored on a 2-tiered scale. CD31 microvessel counts showed significant correlation with tumor stage and patient survival (P < .01). D2-40 LVD demonstrated a significant correlation with LN metastases, lymphovascular invasion, and tumor stage (r = 0.45, r = 0.47, and r = 0.37, respectively) and with shorter disease-free survival. D2-40 detected lymphovascular invasion in 29 of 75 cases, more than with CD31 (23/75) and H&E (18/75). VEGF was expressed in 48 (64%) of 75 cases and was significantly correlated with lymphovascular invasion, LN metastases, and overall survival. Our study showed that angiogenesis and lymphangiogenesis have important roles in the progression of esophageal adenocarcinoma.

Multiple neuroenteric cysts at cerebello-pontine angle and foramen magnum: a case report and review of the literature.

Neuroenteric cysts of the CNS are uncommon benign lesions usually involving the spinal cord or rarely the cerebellopontine angle (CPA). We report a rare example of multiple neuroenteric cysts arising from the CPA and foramen magnum in a 20-year-old Caucasian woman who presented with headaches and dizziness. An MRI showed three separate lesions, not communicating with each other. The first lesion, within the left posterior lateral aspect of the CPA, demonstrated isointensity to gray matter on the fluid-attenuated inversion recovery (FLAIR) sequence. The second lesion, within the left foramen of Luschka at the level of the CPA, demonstrated hyperintensity on the T(2)-weighted sequences, intermediate to slightly hyperintense on T(1)-weighted sequence and hyperintensity on FLAIR. The third lesion, within the anterior/inferior left cerebellum at the level of the foramen magnum, followed CSF signal intensity throughout. None of the lesions demonstrated significant enhancement or bone lesions. Due to compression effect, surgery was performed. Pathologic examination revealed cystic structures lined by a single layer of non-ciliated well-differentiated mucin-producing columnar epithelium with eosinophilic to amphophilic cytoplasm and round to oval nuclei with focal pseudostratification. Immunohistochemical studies showed focal positivity for cytokeratin 7, CK 5/6, synaptophysin, and carcinoembryonic antigen (CEA), diffuse positive staining for epithelial membrane antigen (EMA) and BerEP4; and negative staining for cytokeratin 20, TTF-1, and GFAP. The MIB-1 proliferation index was < 1%. One-year follow-up has shown no recurrence. The differential diagnosis and a brief review of the literature are also presented.