Immunophenotype and K-RAS mutation in mucinous ovarian adenocarcinoma with mural nodule of high-grade sarcoma: case report.

Ovarian mucinous tumors with mural nodules are rare. The mural nodules are microscopically divergent neoplasms of varying sizes that may be benign (eg, sarcoma-like and carcinosarcoma-like), or malignant (eg, anaplastic carcinoma and sarcoma). The K-RAS gene mutation in ovarian mucinous neoplasms with mural nodules has not been previously reported. This is a case report of a 25-year-old female diagnosed with ovarian invasive mucinous adenocarcinoma with mural nodule of high-grade sarcoma. The mucinous tumor component demonstrated a K-RAS codon 12/13 mutation (p.G12V, c.35 G>T), whereas the sarcomatous component demonstrated a K-RAS codon 12/13 mutation (p.G12D, c.35 G>A). Although both tumor components revealed a mutation in codon 12 of K-RAS, they were of different nucleotide substitutions, indicating that these 2 tumor components were of different clonal origins. However, the fact that the 2 mutations identified in the tumor components are the most common mutations reported in mucinous tumors of the ovary, raises the possibility that sarcomatous mural nodules simply represent a form of dedifferentiation in mucinous tumors.

The role of axillary lymph node fine needle aspiration in breast cancer staging prior to chemotherapy with histological correlation.

OBJECTIVE: Axillary lymph node (LN) sampling is important for breast cancer staging and can be performed using fine needle aspiration (FNA). The aim of this study is to review the axillary LN FNAs performed at our institution prior to treatment, and to correlate their results with the available LN histology in order to evaluate the diagnostic utility of FNA. STUDY DESIGN: A total of 130 cases were retrospectively identified over a 1-year period and reviewed. The FNA findings were correlated with the histological findings in 65 (50%) LN core biopsies, 43 (33%) sentinel LN biopsies, and 22 (17%) axillary dissections. RESULTS: One hundred and thirteen FNA cases (89%) correlated with the histology, while 14 cases (11%) did not correlate, including 1 false positive and 13 false negatives. Of the false-negative cases, metastases in the biopsy ranged from isolated tumor cells to 5 mm in the greatest dimension. The overall sensitivity was 85%, specificity 98%, positive predictive value 99%, and negative predictive value 75%. CONCLUSION: Pretherapy staging of breast cancer by FNA is a useful diagnostic modality with a high specificity and positive predictive value. Due to false-negative diagnoses, a negative FNA should be followed up with further LN sampling.

Follow-up outcomes for a large cohort of US women with negative imaged liquid-based cytology findings and positive high risk human papillomavirus test results.

OBJECTIVE: This study aimed to follow a large group of US women with negative computer-imaged liquid-based cytology (LBC) and positive high risk (hr) HPV DNA results. METHODS: Negative LBC and positive hrHPV cases were identified between July 1, 2005 and December 31, 2009. Cytologic and histopathologic follow-up results, repeat HPV results, and prior history were analyzed. RESULTS: 1099 Patients with negative LBC and positive hrHPV results were identified. Eight hundred sixty-nine had repeat Pap or histopathologic follow-up results. Average age was 41.2 years. Average follow-up was 23.2 months. Two hundred ninety of 869 had colposcopic examination and biopsies, including 33 diagnostic excisional procedures and 10 hysterectomies. Cervical intraepithelial neoplasia (CIN) 1 and low-grade squamous intraepithelial lesions (CIN1/LSIL) and more severe lesions (CIN1/LSIL+) were detected in 211 of 689 (24.3%). CIN2+ was diagnosed in 21 (2.4%) (1 VAIN3, 2 adenocarcinoma in situ, 1 invasive cervical adenocarcinoma). Six hundred six had repeat HPV tests and 200 had multiple repeat HPV tests. More LSIL/CIN1+ was identified with repeat positive HPV results than with repeat negative HPV results (P<0.001). LSIL/CIN1+ was detected more often with a history of LSIL/CIN1+ than with a history of negative Paps (P<0.001). Eight of 105 (7.6%) cytology-negative HPV-positive patients tested positive for HPV 16 and/or HPV 18. CONCLUSION: This is the largest study documenting follow-up on US cytology-negative hrHPV-positive patients screened with now widely utilized FDA-cleared methods of ciLBC and hrHPV testing. Of 869 patients followed for an average of almost 2 years, 20 cases of high grade intraepithelial neoplasia (2.3%) and one case of endocervical adenocarcinoma were detected. 90.5%(190/210) of intraepithelial neoplasias detected during follow-up were CIN1.

The spectrum of morphomolecular abnormalities of the E-cadherin/catenin complex in pleomorphic lobular carcinoma of the breast.

Pleomorphic lobular carcinoma of the breast is a high nuclear grade variant of lobular carcinoma. E-cadherin, a tumor-invasion suppressor gene, codes for a transmembrane protein that functions in intercellular adhesion. The E-cadherin protein internal domain binds with alpha, beta, gamma, and p120 catenins to anchor the E-cadherin complex to the actin cytoskeleton of the cell. The E-cadherin gene is routinely mutated in lobular neoplasia. This study examines the morphomolecular spectrum of the components of the E-cadherin-catenin complex in lobular neoplasia. Fifteen cases of pleomorphic lobular neoplasia, 8 cases of classic lobular neoplasia and 4 ductal carcinomas were studied. Normal breast epithelium and invasive ductal carcinomas all showed intense linear cell membrane immunostaining with antibodies to E-cadherin, alpha, beta, gamma, and P120 catenins. Membrane immunostaining of the catenin antibodies in lobular neoplasia was negative, except for rare cases that displayed beaded or dotlike patterns. Cytoplasmic immunostaining patterns for all lobular lesions included coarse paranuclear granules of beta catenin or diffuse intense cytoplasmic staining for P120 catenin. These immunostaining patterns demonstrate that catenins alpha, beta, gamma, and p120 are routinely dislocated from the cell membrane into the cytoplasm in lobular neoplasia and that the disrupted catenin patterns parallel absence of membrane E-cadherin in all cases. The diffuse cytoplasmic immunostaining of p120 in lobular neoplasia may be useful diagnostically as a positive marker for lobular neoplasia.

Clinical significance of cytologic diagnosis of atypical squamous cells, cannot exclude high grade, in perimenopausal and postmenopausal women.

We used cytohistologic correlation to determine the clinical significance of atypical squamous cells, cannot exclude high grade (ASC-H) in perimenopausal and postmenopausal women. A computer search identified 250 Papanicolaou smears from women older than 45 years with a diagnosis of ASC- H. Cases were considered perimenopausal (45 to < 55 years; 150 cases) and postmenopausal ((3)55 years; 100 cases). No follow-up data were available for 33 cases, which were excluded. The remaining 217 cases (perimenopausal, 127; postmenopausal, 90) had surgical or cytologic follow-up. Results of follow-up colposcopic biopsy were available for 176 (81.1%) and cytology for 41 (18.9%) women. Follow-up results were as follows: perimenopausal women, negative, 50 (39.4%); mild dysplasia (low-grade squamous intraepithelial lesion [LSIL]), 46 (36.2%); high-grade dysplasia (high-grade SIL [HSIL]); 28 (22.0%); and ASC of undetermined significance (ASC-US), 3 (2.4%); postmenopausal women, negative, 52 (58%); LSIL, 31 (34%); HSIL, 5 (6%); and ASC-US, 2 (2%). The diagnosis of ASC-H in postmenopausal women usually is associated with LSIL or a negative diagnosis on follow-up, suggesting a less aggressive surveillance and treatment regimen is needed for postmenopausal women with ASC-H.

Cytomorphologic analysis and histological correlation of high-grade squamous intraepithelial lesions in postmenopausal women.

Atrophy-related epithelial changes often pose a diagnostic difficulty during the interpretation of postmenopausal smears. The objectives of this study are to identify the cytomorphologic features of HSIL, in Pap smears of postmenopausal Pap women, and to investigate the possible criteria that could lead to an inaccurate interpretation and false-positive results. Forty Pap smears that were reported as HSIL in postmenopausal women were reviewed. Follow-up cervical biopsies were available on all cases, of which 6 cases were immunostained for MIB-1 and P16. The following cytomorphologic features were evaluated: smear background, degree of cellularity, cellular arrangement, nuclear size, nuclear membrane irregularity, nuclear/cytoplasmic ratio, hyperchromasia, and chromatin pattern. Significant histological abnormalities were present in 35 out of 40 cases. Of those, 22 (55%) cases had high-grade cervical intraepithelial neoplasia (CIN2 or CIN3), 10 (25%) had CIN-1, 5 (12.5%) had reactive changes in the biopsy, and 3 cases had invasive squamous cell carcinoma. The cytomorphologic features that favored HSIL (P < 0.05) included: increased number of abnormal cells, nuclear membrane irregularities, cellular arrangement, and high nuclear/cytoplasmic ratio. Granular background, nuclear size, hyperchromasia, and abnormal chromatin pattern can be associated with reactive and atrophic changes. Our study showed that cytomorphological features favoring HSIL in postmenopausal smears include increased number of abnormal single cells with high nuclear/cytoplasmic ratio and irregular nuclear membrane. Granular background, nuclear enlargement, abnormal chromatin pattern, and hyperchromasia can be seen in reactive changes, and may lead to inaccurate interpretation.

Sclerosing papillary lesion of the breast: a diagnostic pitfall for malignancy in fine needle aspiration biopsy.

Papillary neoplasms of breast constitute a group of lesions that show broad spectrum of morphological changes, ranging from benign to malignant and posing challenges at all diagnostic levels. Some benign papillary lesions may form well-defined solid masses with a dominant sclerosed architecture, known as complex sclerosing papillary lesion or simply sclerosing papilloma. The purpose of this study is to apply the previously published criteria for papillary lesions and to identify the cytomorphologic findings that lead to false-positive diagnosis of these cases. We reviewed the fine needle aspiration biopsies (FNAB) of six histologically proven sclerosing papilloma that were called suspicious or malignant on FNAB. The patient age ranged from 40 to 69, with a mean of (43 +/- 6) yr. Three patients presented with a palpable lump and two patients had history of fibrocystic disease. All six patients had abnormal screening mammograms. FNAB was performed using a 23-gauge syringe attached to a commercial holder. FNA smears were markedly hypercellular with large number of epithelial fragments and papillary clusters, discohesive single cells that are hyperchromatic with mild to moderate nuclear pleomorphism. Bipolar cells were present in all cases, varying from low to abundant. Intraoperative consultation was requested on four cases. Touch preparations were made on two cases and were reported as suspicious based on the cellularity and nuclear atypia. All surgically excised specimens showed sclerosing complex papillary proliferative lesions with epithelial hyperplasia. In conclusion, FNA cytology of this proliferative lesions may be highly cellular and may display cellular atypia similar to breast carcinoma and thus leads to false-positive interpretation.

Pemphigus vulgaris of the vagina--its cytomorphologic features on liquid-based cytology and pitfalls: case report and cytological differential diagnosis.

Pemphigus vulgaris is an autoimmune bullous disease that involves skin and mucous membrane. Although the female genital tract is rarely affected, its cytomorphologic features on a conventional cervicovaginal smear have been notoriously described with a possibility of being misdiagnosed as neoplastic lesions. Its cytological mimicry for squamous cell carcinoma has been described as having serious misdiagnostic potential, particularly if appropriate clinical information is not provided. We report a case of pemphigus vulgaris involving the vagina diagnosed on a liquid-based cervicovaginal smear Thin Prep(R) (TP). The smear was initially reported as squamous cell carcinoma. However, re-evaluation of the TP smear raised the suspicion of pemphigus, which was supported subsequently by clinical information and tissue biopsy confirmation. We described the cytologic features of pemphigus vulgaris on a TP smear and compared them with those of neoplastic conditions. Pemphigus cells on a TP smear exhibit similar cytomorphologic features to those on a conventional smear. Recognizing euchromatin pattern and smooth nuclear contours which may be better appreciated on a TP can prevent overdiagnosis.

Routine endometrial sampling of asymptomatic premenopausal women shedding normal endometrial cells in Papanicolaou tests is not cost effective.

BACKGROUND: Following The Bethesda System 2001 (TBS 2001) recommendation to report normal endometrial cells (nEMC) in women ages >or=40 years, studies have shown that endometrial (EM) sampling has increased, but detection of significant EM pathology has not increased. The cost implications of this increased EM sampling have not been specifically addressed. The aim of this study was to assess the cost effectiveness of EM sampling in women ages >or=40 years with nEMC in their Papanicolaou tests. METHODS: The authors reviewed 499 cases at a large academic women's hospital where nEMC had been reported in Papanicolaou tests followed by EM tissue sampling. Relevant clinical information was obtained from cytopathology and surgical pathology reports. Data on costs of EM sampling were obtained from business offices. RESULTS: Of 1049 women ages >or=40 years who were shedding nEMC, 499 (48%) had follow-up EM sampling. In follow-up EM sampling, 6 cases of significant pathology (atypical complex EM hyperplasia or adenocarcinoma) were detected. Asymptomatic women totaled 350, and the total cost for EM sampling of asymptomatic patients shedding nEMC was estimated at 107,272 dollars. Three of the asymptomatic patients had significant EM pathology, but all 3 were postmenopausal. Three additional premenopausal patients with significant pathology were symptomatic with vaginal bleeding. CONCLUSIONS: No asymptomatic premenopausal patients shedding nEMC either before or after Day 12 of their menstrual cycle were found to have significant EM pathology in this large study of almost 500 women with nEMC in their Papanicolaou tests. The total costs, when projected nationally, for EM sampling in asymptomatic premenopausal women were highly significant. Educational discussions with clinicians in this community are underway to reduce the number of women who undergo EM sampling after Papanicolaou test findings of nEMC. Routine EM sampling of asymptomatic premenopausal women with nEMC in Papanicolaou tests is not cost-effective.

Clinical implications of the diagnosis "atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion" in pregnant women.

BACKGROUND: Atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) has a high predictive value for high-grade intraepithelial lesion (HSIL) in the general population. However, the significance of ASC-H in pregnant women remains to be elucidated. The objective of this study was to investigate the clinical implications and pathologic significance of ASC-H in pregnant women, so that these patients will be managed appropriately. METHODS: All Papanicolaou tests that were diagnosed as ASC-H in pregnant women over 1.5 years (total, 60 women) were reviewed and correlated with histologic and/or cytologic follow-up. High-risk type of human papillomavirus (HPV) status was also correlated with follow-up findings. The following cytomorphologic parameters were evaluated for each woman and were compared between the squamous intraepithelial lesion (SIL) follow-up group and the benign follow-up group: inflammatory background, the number of atypical cells, cell arrangement pattern, nuclear irregularity/grooves, hyperchromasia, and cell shape. RESULTS: Among 30 women who had histologic follow-up, 3 women (10%) had HSIL, and 13 women (43%) had low-grade intraepithelial lesion (LSIL). Among 32 women who had cytologic follow-up, 2 women (6%) had HSIL, 3 women (9%) had LSIL, 1 woman (3%) had ASC-H, and 3 women (9%) had atypical squamous cells of undetermined significance (ASCUS). HPV was detected in 24 of 43 women (56%). The cytomorphologic features were similar in the SIL follow-up group and the benign follow-up group. No specific cytomorphologic features that predicted underlying SIL were identified. CONCLUSIONS: ASC-H in pregnant women had a lower predictive value for an underlying HSIL compared with the general population. A positive HPV test result was not a good indicator for an underlying SIL, but a negative result appeared to be useful for ruling out an underlying HSIL. Because of low positive predictive value for HSIL and the difficult colposcopic examination, a more conservative follow-up may be reasonable for pregnant women who have a diagnosis of ASC-H. HPV testing may be used as an adjunctive test.