CDX-2 expression in pulmonary fine-needle aspiration specimens: a useful adjunct for the diagnosis of metastatic colorectal adenocarcinoma.

CDX-2 is a homeobox gene, which encodes a transcription factor that plays a vital role in the development and differentiation of intestinal epithelial cells. Recent studies showed that CDX-2 protein expression by immunohistochemistry (IHC) has a high predictive value for confirming the diagnosis of colorectal adenocarcinoma (ACA). The differentiation of primary pulmonary ACA from metastatic colorectal ACA can be extremely challenging on fine-needle aspiration (FNA). The results of immunostains for TTF-1, CK 7, and CK 20 may be controversial in the differential diagnosis. In this study, we evaluated the clinical utility of CDX-2 in lung FNA specimens. Cell blocks from 41 primary lung and 20 colorectal ACAs metastatic to the lungs were retrieved. Cell block sections were immunostained with a CDX-2 monoclonal antibody. Sensitivity and specificity of CDX-2 for colorectal ACA was 75 and 100%, respectively. All five cases negative for CDX-2 were moderately to poorly differentiated colorectal ACAs. Our study confirms that CDX-2 is a highly useful immunohistochemical marker for the differentiation of primary pulmonary ACA from colorectal ACA metastatic to the lungs in FNA specimens. Of diagnostic importance is the loss of CDX-2 immunoreactivity in poorly differentiated colorectal ACAs.

Effect of Bethesda 2001 on reporting of atypical squamous cells (ASC) with special emphasis on atypical squamous cells-cannot rule out high grade (ASC-H).

We compared the overall ASC rate and the outcomes for women with different categories of ASC before and after TBS 2001 to evaluate the impact of TBS 2001. Our laboratory reported ASC in four subcategories before TBS 2001; ASC, favor reactive (ASC-R), favor low-grade squamous intraepithelial lesion (SIL) (ASC-L), undetermined significance (ASC-US), and ASC-H. Since the implementation of TBS 2001, we have been reporting ASC as ASC-US and ASC-H. After TBS 2001, our ASC rate decreased from 6.2% to 4% (P < 0.0001). Before TBS 2001, ASC-R carried the same risk as ASC-US for underlying condyloma/CIN 1. Moreover, ASC-R was rarely associated with CIN 2 or 3. Before TBS 2001, ASC-H captured more low-grade (condyloma/CIN 1) and less high-grade (CIN 2, 3, and SCC) lesions compared to after TBS 2001. More women with ASC-H after TBS 2001 underwent colposcopy (80% vs. 71%, P < 0.05). Twenty-two percent of women with ASC-H required 2-4 colposcopies to identify the high-grade lesion. Our results confirm that consistent application of TBS 2001 terminology for ASC reduces the ASC rate, and better identifies women at high risk for CIN 2, 3, and SCC. In addition, ASC-H requires very close clinical follow-up as a significant percentage of women require more than one colposcopy to identify the high-grade lesion.

Cytomorphology of benign breast disease.

Fine needle aspiration biopsy is a widely used technique for the initial diagnosis of mammary lesions. The majority of patients undergoing fine needle aspiration biopsy of a breast lesion will have a benign disease of the breast. This article provides a review of the cytomorphologic features in a variety of benign breast lesions,and discusses the commonly encountered differential diagnoses on aspiration biopsy. Topics discussed include inflammatory and reactive conditions, treatment-induced changes, pregnancy-related changes, benign proliferative lesions, and benign neoplasms of the breast.

Atypical repair on Pap smears: clinicopathologic correlates in 647 cases.

The Bethesda system separates atypical reparative changes (ARC) from "typical" repair and places it into the atypical squamous cells of undetermined significance (ASC-US) category. The cytologic diagnosis of ARC represents both diagnostic and management challenges because its clinical significance is controversial and has not been fully investigated. On the basis of scant literature on follow-up of women with ARC on Papanicolaou (Pap) test, we reviewed data from our patient population, which consists of a mixture of low- and high-risk women. Six hundred forty-seven patients with ARC on their Pap tests were identified in a 7-yr period. Of this, 189 (29%) women were lost to follow-up. Of the 458 women with follow-up, 31% had cervical biopsies and 69% were followed by repeated Pap tests. The age ranged from 16 to 86 (mean 47 yr). The incidence of squamous intraepithelial lesion was 5.2% (5% low-grade and 0.2% high-grade). Most women (62%) with ARC on Pap test had a benign condition on follow-up. For some women, the immediate cause was not known and the Pap abnormality resolved spontaneously. Our study questions the validity of reporting ARC within the ASC-US category.

Atypical papillary proliferation in gynecologic patients: a study of 32 pelvic washes.

Papillary clusters in gynecologic pelvic washes frequently cause diagnostic challenges because they can be associated with borderline or malignant ovarian tumors, as well as benign pelvic diseases. The objective of our study was to review all pelvic washes with atypical papillary proliferation (APP) and investigate whether cytomorphology and/or immunohistochemistry on cell block could determine their origin. Thirty-two pelvic washes from 31 patients containing APP were reviewed and correlated with their corresponding gynecologic or pelvic disease. Previously obtained cell blocks with immunohistochemical (IHC) stains were reviewed also. Nine of 32 washes (28%) were overcalled as malignant and were from patients with 5 borderline serous ovarian tumors (BSTO), 1 ovarian follicular cyst, 1 serous cystadenofibroma, and 1 endometrial carcinoma with ovarian seromucinous cystadenoma. BSTO and endometriosis were the most common sources of APP. Cell blocks could not discriminate further the etiology of APP. Immunohistochemistry was performed rarely and not fully contributory. Caution in interpreting papillary groups and cytohistological correlation is recommended to prevent a high false positive rate.

Aspiration biopsy of nodular pseudoangiomatous stromal hyperplasia of the breast: clinicopathologic correlates in 10 cases.

Nodular pseudoangiomatous stromal hyperplasia (PASH) of the breast is rare and often indistinguishable from fibroadenoma, clinically and on aspiration biopsy smears. We report our observations in 10 patients with PASH, evaluated by fine-needle aspiration (FNA) biopsy and core biopsy. We retrospectively reviewed the clinical, radiographic, cytologic, and histologic findings in 10 cases of pure nodular PASH. Ten patients with a presumed clinical and radiologic diagnosis of fibroadenoma underwent aspiration biopsy. The aspiration smears were diagnosed as fibroadenoma (4 cases), cellular fibroadenoma (1 case), schwannoma versus neurofibroma (1 case), fibrocystic change (3 cases; 2 with atypia), and "not specific for a lesion" (1 case). A diagnosis of PASH was not suspected in any case. A discrepant or imprecise cytologic diagnosis and/or the presence of dissociated spindle or epithelial cells, or cellular stromal fragments prompted a surgical excision in 7 of 10 patients (70%). The remaining 3 patients exhibited cytologic features of fibroadenoma and were diagnosed as such; however, surgical excision was recommended. Three patients underwent a subsequent core biopsy, with a diagnosis of PASH being made in 1 patient. FNA biopsy could not discriminate PASH from fibroadenoma in 4 of 10 patients (40%) or suggest a diagnosis of PASH in any case. On retrospective review, the finding of plump, spindle-shaped mesenchymal cells may be a cytologic clue to suggest a diagnosis of PASH.

Metastases to the kidney: eleven cases diagnosed by aspiration biopsy with histological correlation.

Metastases to the kidney from extrarenal primary tumors are uncommon and may mimic renal-cell carcinoma clinically when presenting as a single mass with hematuria. Fine-needle aspiration biopsy (FNAB) is a useful diagnostic method for the evaluation of primary renal tumors. Only a few studies have investigated the value of cytological evaluation of secondary renal tumors. We report our experience with these tumors. Eleven cases of extrarenal primary tumors metastatic to the kidney, diagnosed by aspiration biopsy with histological correlation, are discussed. The diagnosis of metastatic disease to the kidney was accurately made by aspiration biopsy. Knowledge of the patients' history, histological correlation with the primary tumor, and the radiological characteristics of the renal masses were helpful in achieving a correct diagnosis. FNA cytology (FNAC) is an accurate method for the diagnosis of tumors metastatic to the kidney. Distinction between primary and secondary tumors of the kidney is crucial to guide management and prevent unnecessary surgery.

Stellate-cell lipidosis in liver biopsy specimens. Recognition and significance.

Hepatic stellate-cell lipidosis due to hypervitaminosis A can lead to cirrhosis, which can be averted by restricting vitamin A intake. Other causes, including the use of synthetic retinoids, have been postulated. We studied the frequency and etiology of stellate-cell lipidosis in patients undergoing liver biopsy for reasons other than vitamin A abuse. Fourteen cases (1.1%) were identified retrospectively among 1,235 nontransplant liver biopsy specimens examined from January 1995 through December 1999. Diagnostic criteria included the following: lipid-laden cells in the space of Disse; small, dark, crescent-shaped nuclei with inconspicuous nucleoli; and wispy cytoplasmic strands separating fat droplets. Patient details, reason for biopsy, and medication use were studied. Reasons for biopsy included hepatitis C (10 cases), abnormal liver enzyme levels (2 cases), methotrexate use (1 case), and alcohol abuse (1 case). Hypervitaminosis A was not suspected clinically in the 5 patients who used oral vitamin A or 3 who used topical tretinoin (Retin-A). In 6 patients, no cause of stellate-cell lipidosis was discerned. Stellate-cell lipidosis should be reported to alert clinicians to a potentially preventable form of liver injury.

Rhabdoid epithelioid leiomyosarcoma of the uterine corpus: a case report and literature review.

A case of epithelioid leiomyosarcoma of the uterus with rhabdoid phenotype and early rhabdomyoblastic differentiation is described. A 72-year-old woman with a 5-week history of increased abdominal girth was found to have a large pelvic mass. The uterus revealed a large intramyometrial and left adnexal necrotic tumor that had spread to the small bowel mesentery and to the anterior abdominal peritoneum. The tumor was an epithelioid leiomyosarcoma with rhabdoid phenotype and focal early rhabdomyoblastic differentiation, as confirmed by immunohistochemical and ultrastructural techniques. Also called composite extrarenal rhabdoid tumor (CERT), this lesion should be differentiated from malignant mixed müllerian tumor, rhabdomyosarcoma, endometrial stromal sarcoma, and pure rhabdoid tumors of the uterus. The recognition of a rhabdoid phenotype is of clinical importance since these tumors are prone to be aggressive.

Significance of the cytologic diagnosis of endocervical glandular involvement in high-grade squamous intraepithelial lesions.

The cytologic criteria for the diagnosis of endocervical gland involvement (EGI) by high-grade squamous intraepithelial lesions (HGSILs) have been described, and this diagnosis occasionally is made. This study evaluates the accuracy of a cytologic diagnosis compared with that of follow-up cone biopsies. Twenty-eight patients with Papanicolaou (Pap) smear diagnoses of HGSILs with EGI, with follow-up cone biopsies, were identified from New York University computerized files. Results were compared with those of a control group of 28 patients showing cervical intra-epithelial neoplasia grades II/III (CIN-II/III), irrespective of previous Pap smear findings. On subsequent cone biopsy samples, 26 of the 28 study cases showed signs of HGSIL. Of these 26 patients, 17 (65%) showed evidence of HGSIL with EGI. Among the 28 control cases, 20 (71.4%) had EGI on the cone biopsies (P = NS). We also examined previous Pap smear findings in a control group of 42 cone biopsies with CIN-II or CIN-III, with or without EGI. EGI was diagnosed in previous Pap smears in 3 of the 31(10%) cases that showed signs of EGI on cone biopsies and in 2 of the 11 cases (18%) that did not evidence EGI on subsequent cone biopsies (P = NS). In our experience, the cytologic diagnosis of EGI on Pap smears did not identify a group of patients with increased frequency of EGI on subsequent cone biopsies.

Role of fine-needle aspiration cytology in breast lymphoma.

Lymphomas of the breast are rare and may mimic carcinoma clinically. We investigated the ability of fine-needle aspiration (FNA) biopsy combined with adjunctive flow cytometry (FC), immunofluorescence microscopy (IFM), and immunocytochemistry (ICH) to diagnose and eventually subclassify lymphomas of the breast according to the Revised European American Lymphoma/World Health Organization classification. We retrieved 21 breast aspirates from 19 patients with a cytologic diagnosis of lymphoma or plasmacytoma over a 10-year period (1992-2002), excluding 98 benign intramammary lymph nodes and 1 atypical lymphohistiocytic proliferation (Rosai Dorfman disease). FC was performed in 15/21 aspirates, IFM in 1/21, ICH in 3/21. Histologic follow-up (HF) was obtained for 10 patients, most of them with primary lymphoma. For the remaining nine patients without HF, flow cytometric analysis, comparative morphology, or remission after chemotherapy regimens supported the cytologic diagnosis. Of 19 patients, 11 patients had a secondary lymphoma (SL) and 8 patients had a primary lymphoma (PL). FNA and FC/IFM/ICH classified 7/8 PLs as B-cell lymphomas and 1/8 PLs as plasmacytoma. However, FNA could only subclassify 3 of 8 PLs. FNA and/or FC subclassified accurately 10/11 SLs. All cases were accurately immunophenotyped as B-, T-cell non-Hodgkin's lymphomas or plasmacytoma. World Health Organization classification was achieved in 3/8 PLs (42%) and 10/11 SLs (91%; P = 0.04). Subclassification (which has an impact on long-term management and prognosis) was significantly better in SL, when a previous histologic diagnosis had already been made, when compared to PL, of which 5/8 cases (62.5%) could not be accurately classified.

False-positive squamous cell carcinoma in cervical smears: cytologic-histologic correlation in 19 cases.

Cytologic features of squamous intraepithelial lesions (SIL) can mimic those of invasive squamous-cell carcinoma. We compare and correlate the cytological findings of 19 false-positive squamous-cell carcinomas with follow-up cone biopsies or hysterectomy specimens to define which type of dysplasia is more prone to diagnostic errors on cervical Papanicolaou (Pap) smears. Out of 128 patients diagnosed with invasive squamous-cell carcinoma from 1994-2000, 19 (14.8%) with follow-up cone biopsies or hysterectomy specimens were false-positive cases, showing only cervical intraepithelial neoplasia (CIN). We reviewed tissue sections from these 19 cases of CIN for cytologic features of squamous-cell carcinoma, such as markedly pleomorphic and/or dysplastic squamous cells, necrosis, and nucleoli. Twelve of 19 patients (63%) were menopausal. The mean age was 50.5 yr. On review of cervical smears, 18 cases qualified for the cytologic diagnosis of squamous-cell carcinoma, keratinizing type, and one case qualified for squamous-cell carcinoma, nonkeratinizing type. Pleomorphic and/or keratinizing dysplasia was found in 15 out of 19 patients (79%), necrosis within superficial endocervical glands in 9 out of 19 patients (47%), and conspicuous nucleoli in 12 out of 19 patients (63%). One or more of these changes were seen in all but 2 patients (89%). Endocervical gland involvement was present and extensive in 18 of the 19 cases (94%). The mean age was older than expected for SIL (50.5 vs. a reported 40), and matched the mean age found in patients with invasive squamous-cell carcinoma. Pleomorphic and/or keratinizing dysplasia involving endocervical glands may exhibit the cytologic features of squamous-cell carcinoma on cervical Pap smears.

Cytological diagnosis of cystic brain tumors: a retrospective study of 88 cases.

The stereotaxic aspiration of cystic brain tumors is performed to provide cyst decompression and/or to facilitate surgical resection. The purpose of our study was to determine the diagnostic value of brain cyst fluid cytology, especially in clinically suspected recurrent tumors with no histological follow-up (HF), when a diagnosis is most needed. We reviewed the cytological diagnoses of 88 aspirates from 70 patients with cystic brain tumors between 1995 and 2001, of which 31 had a prior known malignancy including 18 primary brain tumors (PBTs) and 13 adenocarcinomas (ACAs). Sixty-nine of 88 aspirates were obtained intraoperatively. Nineteen of 88 aspirates were obtained from 10 patients with recurrent or persistent cystic brain tumors (8 patients with PBT and 2 patients with ACA), with available clinicoradiological correlation (magnetic resonance imaging/computed tomography [MRI/CT] scans) in 13 of them. The 88 aspirates were classified in three categories: 28 positive (32%), 15 atypical (17%), and 45 negative (51%). Eight of 28 positive cases (5 case of PBT, 2 cases of ACA, and 1 case of melanoma) were given a nonspecific diagnosis of malignant neoplasm (9% of all cases). Fifteen of 28 positive cases (6 cases of PBT, 8 cases of ACA, and 1 case of melanoma) were diagnosed correctly and confirmed by HF (17% of all cases). Four of 28 cases were ACA diagnosed solely by cytology (<4% of all cases). One neurocytoma (1/28) case was mistaken for an oligodendroglioma despite cell blocks (CBs) and immunophenotyping (IPT) (<1% of all cases). Eleven of 15 atypical cases were 8 cases of PBT, 2 cases of ACA, and 1 case of postoperative change (PC). Four of 15 atypical cases (from three patients with suspected PBT recurrence) could not be further characterized by CB/IPT and had no HF. Twenty-seven of 45 negative cases were falsely negative (23 cases of PBT, 3 cases of ACA, and 1 case of malignant neoplasm); 11/45 cases were PC, and 7/45 (from five patients with clinically suspected tumor recurrence) cases had no HF. Cytological evaluation of brain cyst fluid is not a reliable means of diagnosing cystic brain neoplasms (including recurrences) due to a high false negative rate and a low sensitivity. Most of the negative or atypical cases (68% of all cases) were recurrent PBT of glial origin that may not be prone to exfoliate. These cytological specimens consisted of lysed blood, obscuring inflammatory cells, and degenerated diagnostic cells if any, yielding inconclusive results.

Aspiration cytology of cystic carcinoma of the breast.

Cystic carcinomas of the breast are rarely encountered in fine-needle aspiration (FNA) biopsies. The most common entities comprise intracystic papillary adenocarcinoma, ductal adenocarcinoma with cystic degeneration including comedo forms of ductal adenocarcinoma in situ, medullary carcinoma, squamous carcinoma, and cystic hypersecretory ductal adenocarcinoma. The cytologic diagnosis is often hampered by sparse cellularity, abundant obscuring blood, necrotic debris, and degenerative changes in diagnostic cells. We report on the cytologic features of 10 cases of cystic carcinoma, including 12 FNA biopsies with radiologic and surgical correlation. The original cytologic diagnoses for these cases were: benign (2 cases), atypical (2 cases), suspicious (3 cases), and positive for malignant cells (3 cases). On repeat FNA, one benign case and one atypical case were reclassified, respectively, as atypical and suspicious for carcinoma. The follow-up diagnoses were 5 intracystic papillary adenocarcinomas and 5 cystic ductal adenocarcinomas. Despite 2 false-negative cases, all cases were adequately managed. Correlation with clinical and radiologic findings and direct sampling of any solid component of these cystic neoplasms are crucial in diagnosis and management.

Pleomorphic liposarcoma of the uterus: case report and literature review.

A 62-year-old woman with a history of breast carcinoma being treated with tamoxifen presented with a rapidly enlarging pelvic mass. Imaging studies suggested a uterine leiomyoma with possible sarcomatous transformation. Laparotomy revealed a 15-cm, oval, well-circumscribed mass emanating from the posterior cervix and left uterosacral ligament. The tumor had a variegated fleshy, tan, myxoid, and necrotic sectioned surface. Microscopic examination revealed a variety of patterns and cell types characteristic of liposarcoma that included myxoid/round cell, storiform/pleomorphic, epithelioid, and spindle cell areas. Lipogenic areas exhibited a "crow's feet" vasculature and characteristic lipoblasts. The tumor cells were highly pleomorphic with numerous mitotic figures, some of them atypical. The tumor cells were immunoreactive for vimentin, estrogen receptors, and S-100. The tumor recurred 9 months postoperatively. Although a variety of uterine tumors have been associated with tamoxifen treatment, this appears to be the first example of tamoxifen-associated uterine liposarcoma.