Malignancy associated with ovarian teratomas: frequency, histotypes, and diagnostic accuracy of intraoperative consultation.

Mature cystic teratomas are common ovarian germ cell tumors that rarely undergo malignant transformation, and intraoperative consultation is generally not warranted. The aims of this study were to review a large number of ovarian teratomas (OTs), to document the rate and histotypes of associated malignancy, and to identify parameters that may be associated with malignancy. In this study, a retrospective medical record review of patients diagnosed as having OTs from 2002 to 2011 was performed. Patient age, tumor size, type, and laterality were obtained from pathology reports and operative notes. A total of 956 OTs that ranged in size from 0.3 to 45 cm were identified. Intraoperative consultation was requested in a total of 316 (33.1%) of 956. Intraoperative gross evaluation only was performed on 211 (66.8%) of 316, of which 4 cases were malignant on final diagnosis. Frozen section was performed on 105 (33.2%) of 316, of which 12 were malignant on final diagnosis. The final diagnoses of all OT cases were as follows: 26 (2.7%) of 956 were associated with malignant tumors. The latter were larger than benign cases (average sizes, 11.2 cm vs 6.5 cm; P < .001), and patients with malignant tumors were significantly older than those with benign mature cystic teratoma (48.7 years vs 38.8 years, P < .001). The sensitivity and positive predictive value of frozen section examination during the intraoperative consultation for the detection of malignancy in OTs are 80% and 100%, respectively. In conclusion, patient age and large tumor size were associated with malignancy in this data set. Mucinous and serous borderline tumors were more common than squamous cell carcinoma in our cohort.

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.

Nucleotide excision repair deficiency is intrinsic in sporadic stage I breast cancer.

The molecular etiology of breast cancer has proven to be remarkably complex. Most individual oncogenes are disregulated in only approximately 30% of breast tumors, indicating that either very few molecular alterations are common to the majority of breast cancers, or that they have not yet been identified. In striking contrast, we now show that 19 of 19 stage I breast tumors tested with the functional unscheduled DNA synthesis assay exhibited a significant deficiency of DNA nucleotide excision repair (NER) capacity relative to normal epithelial tissue from disease-free controls (n = 23). Loss of DNA repair capacity, including the complex, damage-comprehensive NER pathway, results in genomic instability, a hallmark of carcinogenesis. By microarray analysis, mRNA expression levels for 20 canonical NER genes were reduced in representative tumor samples versus normal. Significant reductions were observed in 19 of these genes analyzed by the more sensitive method of RNase protection. These results were confirmed at the protein level for five NER gene products. Taken together, these data suggest that NER deficiency may play an important role in the etiology of sporadic breast cancer, and that early-stage breast cancer may be intrinsically susceptible to genotoxic chemotherapeutic agents, such as cis-platinum, whose damage is remediated by NER. In addition, reduced NER capacity, or reduced expression of NER genes, could provide a basis for the development of biomarkers for the identification of tumorigenic breast epithelium.

Mucinous tumors of the ovary: diagnostic challenges at frozen section and clinical implications.

OBJECTIVE: Frozen section (FS) diagnosis of mucinous tumors of the ovary can be quite difficult due to the size of these tumors, heterogeneity and potential risk of metastasis from gastrointestinal (GI) neoplasms. Given the paucity of data on this subject, our objective was to determine the reliability of FS diagnosis in ovarian mucinous tumors. METHODS: A retrospective review of 73 consecutive ovarian mucinous tumors submitted for frozen section (FS) evaluation between January 2004 and November 2009 was conducted. FS and final pathology results, in addition to patient characteristics, were collected. Univariate analysis was performed evaluating predictors of FS reliability. RESULTS: The average tumor size was 19.7cm (0.8-50cm). The FS and final pathology diagnosis were concordant in 66% (48/73) of the cases. Of the 25 (34%) discordant cases, 8 (11%) were downgraded and 17 cases (23%) were upgraded. Of the 44 tumors interpreted as LMP on FS, 14 (32%) were malignant at final diagnosis (26% ovarian, 7% GI) and 8 (18%) were benign. Of the 23 benign tumors on FS, 13% were upgraded to either LMP or malignant at final diagnosis. Tumors with a malignant diagnosis on FS were 100% concordant with final diagnosis. Univariate analysis did not reveal any correlation with the FS diagnosis and patient age, tumor size or presence of bilateral disease. CONCLUSIONS: Our study showed a 34% rate of discordance between FS and final diagnosis. Given that 5 cases (7%) were of GI origin, intraoperative assessment of the appendix should be performed in all mucinous ovarian 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.

Percent surface area involvement is a predictor of lymph node metastasis in endometrial cancer.

OBJECTIVE: To determine if percent surface area involvement (SAI) of tumor in endometrial cancer is predictive of lymph node metastasis. METHODS: A retrospective study was performed of all patients diagnosed with endometrial cancer at Magee Women's Hospital between January 1990 and December of 1995. Papillary serous and clear cell histologic subtypes were excluded. Pathology reports were reviewed for percent SAI, myometrial invasion, grade, histologic subtype, lymphovascular space invasion, and lymph node metastasis. Percent SAI was categorized into three groups: <35%, 35-80%, and >80%. The primary outcome variables were pelvic or periaortic lymph node metastasis. Univariate and multivariate analysis logistic regression models were used to determine predictors of nodal metastasis. RESULTS: Of 558 patient records reviewed, 319 had lymph node dissections performed and 42 (13%) of those patients had positive lymph nodes. Two of 79 (3%) patients with <35% SAI had lymph node metastasis, 17 of 165 (10%) patients with 35-80% SAI had lymph node metastasis, and 23 of 75 (31%) patients with >80% SAI had lymph node metastasis. The percent SAI was significantly associated with lymph node metastasis (p<0.001). Multivariate logistic regression indicated that for patients with >80% SAI, the odds of having lymph node metastasis were 10.8 times (CI 1.3-90.4) that for patients with similar tumor histology, grade, and invasion, but <35% SAI (p=0.03). A subset analysis of patients with superficial myometrial invasion was performed and 16% of patients with <50% myometrial invasion and >80% SAI had positive lymph nodes, while only 1.4% of patients with <50% myometrial invasion and <35% SAI had positive lymph nodes (p=0.02). CONCLUSION: Our analysis indicates that percent SAI is an independent risk factor for lymph node metastasis. Furthermore, assessing SAI with myometrial invasion gives a more accurate prediction of lymph node metastasis than myometrial invasion alone. This becomes clinically relevant when assessing risk factors for lymph node metastasis intraoperatively.

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.

Primary Pure Endometrial Primitive Neuroectodermal Tumors with EWSR1 Gene Rearrangement: Report of 2 Cases.

Primary Primitive Neuroectodermal Tumor (PNET) of the female genital tract is very rare. The majority has been described in ovaries, and the endometrium is an even rarer site. Herein we describe 2 cases of primary uterine corpus PNET cases with EWSR1 FISH confirmation. To the best of our knowledge, there are four cases reported in the English literature. The knowledge of these tumors' incidence in the endometrium is important to keep in mind, to differentiate it from poorly differentiated and undifferentiated adenocarcinomas, should such pattern of growth be encountered.

Subcutaneous Leiomyosarcoma Metastasized to the Lymph Nodes Involved with Small Lymphocytic Lymphoma / Chronic Lymphocytic Leukemia.

Herein, we present a case of a 76-year-old Caucasian man with a very large fungating, ulcerating mass, involving the right neck and parotid area, which developed while he was being treated for chronic lymphocytic leukemia/small lymphocytic lymphoma. Resection of the fungating right neck tumor, right modified radical neck dissection, and right superficial parotidectomy with flap reconstruction were performed. The final pathological diagnosis was high-grade leiomyosarcoma of the skin and the subcutaneous tissue, with invasion into the skeletal muscle, skin, and soft tissue. Additionally, the sarcoma had metastasized to the lymph nodes that were involved diffusely by lymphoma. The most interesting fact for this case is coincidence of three rare occurrences which were soft tissue sarcomas of subcutaneous leiomyosarcoma form and its metastasis to same lymph nodes that were involved with lymphoma.

The importance of tattoo pigment in sentinel lymph nodes.

BACKGROUND: The presence of pigment in axillary lymph nodes (LN) secondary to migration of tattoo ink can imitate the appearance of a blue sentinel lymph node (SLN) on visual inspection, causing the operator to either miss the true SLN or excise more than is needed. OBJECTIVE: We present patients with tattoos ipsilateral to an early stage breast cancer who underwent a SLN biopsy. METHODS: Patients were retrospectively reviewed from medical records and clinicopathologic data was collected. A total of 52 LNs were retrieved from 15 patients for sentinel mapping and 29 of them had tattoo pigmentation on pathologic evaluation. RESULTS: Of those 29 SLNs, 2 of them (6.9%) were pigmented, but did not contain either blue dye or Tc-99m (pseudopigmented SLN). Two (3.8%) SLNs were positive for metastasis; both of these had either blue dye or Tc99m uptake, and 1 demonstrated tattoo pigment in the node. CONCLUSIONS: In this cohort of patients with ipsilateral tattoos, removed more LNs lead to unnecessary excision which may important for increasing the risk of arm morbidity from SLN biopsy. However, the presence of tattoo pigment did not interfere with understaging for axillary mapping and it did not effect of pathological identification of SLNs positivity.

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.

The role of molecular biomarkers for predicting adjacent breast cancer of Atypical Ductal Hyperplasia diagnosed on core biopsy.

BACKGROUND: Atypical Ductal Hyperplasia (ADH) is a disease of the proliferative breast lesion characterized with atypia and when diagnosed on core needle biopsy (CNB), excisional biopsy is the current management to exclude adjacent cancer, which may found 10 to 20%. OBJECTIVE: The purpose of the study is to investigate the role of biomarkers on surgical decision after the diagnosis of ADH on CNB. METHODS: Patients with pure ADH on core biopsy were retrospectively selected, and categorized according to final pathology after excision into three groups: Group I (n: 39) ADH; Group II (n: 27) ductal carcinoma in situ (DCIS), and Group III (n: 9) invasive cancer (IC). Immunohistochemical analyses were performed using biomarkers MUC1, Ki67, Cyclin B1, and Cyclin D1. RESULTS: Only Cyclin D1 was significant in between group analysis by one-way ANOVA (64.74, 49.44, and 51.11, respectively; p= 0.01). However when appropriate cut-off levels (2%-50%) were used for each biomarkers using X2 test, no statistical significance was found. CONCLUSION: MUC1, Ki67, Cyclin B, and Cyclin D1have failed to predict adjacent cancer on core biopsy specimens with ADH. Further surgery is warranted for all ADH cases diagnosed on core biopsies until a new predictor is identified.

Haploinsufficiency for BRCA1 is associated with normal levels of DNA nucleotide excision repair in breast tissue and blood lymphocytes.

BACKGROUND: Screening mammography has had a positive impact on breast cancer mortality but cannot detect all breast tumors. In a small study, we confirmed that low power magnetic resonance imaging (MRI) could identify mammographically undetectable tumors by applying it to a high risk population. Tumors detected by this new technology could have unique etiologies and/or presentations, and may represent an increasing proportion of clinical practice as new screening methods are validated and applied A very important aspect of this etiology is genomic instability, which is associated with the loss of activity of the breast cancer-predisposing genes BRCA1 and BRCA2. In sporadic breast cancer, however, there is evidence for the involvement of a different pathway of DNA repair, nucleotide excision repair (NER), which remediates lesions that cause a distortion of the DNA helix, including DNA cross-links. CASE PRESENTATION: We describe a breast cancer patient with a mammographically undetectable stage I tumor identified in our MRI screening study. She was originally considered to be at high risk due to the familial occurrence of breast and other types of cancer, and after diagnosis was confirmed as a carrier of a Q1200X mutation in the BRCA1 gene. In vitro analysis of her normal breast tissue showed no differences in growth rate or differentiation potential from disease-free controls. Analysis of cultured blood lymphocyte and breast epithelial cell samples with the unscheduled DNA synthesis assay (UDS) revealed no deficiency in nucleotide excision repair (NER). CONCLUSION: As new breast cancer screening methods become available and cost effective, patients such as this one will constitute an increasing proportion of the incident population, so it is important to determine whether they differ from current patients in any clinically important ways. Despite her status as a BRCA1 mutation carrier, and her mammographically dense breast tissue, we did not find increased cell proliferation or deficient differentiation potential in her breast epithelial cells, which might have contributed to her cancer susceptibility. Although NER deficiency has been demonstrated repeatedly in blood samples from sporadic breast cancer patients, analysis of blood cultured lymphocytes and breast epithelial cells for this patient proves definitively that heterozygosity for inactivation of BRCA1 does not intrinsically confer this type of genetic instability. These data suggest that the mechanism of genomic instability driving the carcinogenic process may be fundamentally different in hereditary and sporadic breast cancer, resulting in different genotoxic susceptibilities, oncogene mutations, and a different molecular pathogenesis.

Defining the lymphatic system of the anterior abdominal wall: an anatomical study.

BACKGROUND: Studies describing recent abdominoplasty modifications have reported a decreased incidence of seroma, attributed to preservation of abdominal lymphatics. However, there are limited anatomical data to support this hypothesis. The authors sought to characterize the lymphatic architecture of the abdominal wall and provide a conceptual basis for further refinement of abdominoplasty techniques. METHODS: Fifteen tissue samples from five patients undergoing abdominoplasty were sectioned and analyzed. Slides were stained with hematoxylin and eosin, CD31, and D2-40 and assessed by a pathologist and a plastic surgeon for the presence and number of lymphatics. Results were reported as mean percentage of lymphatic-specific antibody per analyzed area. RESULTS: Lymphatic vessels were observed in the dermis, superficial fascia, and loose areolar tissue but not in deep or superficial fat. The highest concentration was in the dermis (mean, 82.6 percent; range, 69 to 89.2 percent). The Scarpa fascia contained 9.4 percent of lymphatics (range, 7.0 to 11.4 percent), whereas the loose areolar tissue at the specimen base contained an average of 7.9 percent (range, 2.6 to 19.5 percent). These lymphatics were consistently located in the deepest third, with the Scarpa fascia lying an average of 34 percent of the total tissue thickness above muscle fascia. Lymphatic prevalence did not increase in specimens near the superficial epigastric vessels. CONCLUSIONS: Abdominoplasty flap lymphatics are most common in the dermis, with a significant proportion (approximately 17 percent) also appearing near fascial layers. This confirms the presence of deep lymphatic channels that could potentially be preserved during abdominoplasty or lipoabdominoplasty.

Analysis of p53 mutations in cells taken from paraffin-embedded tissue sections of ductal carcinoma in situ and atypical ductal hyperplasia of the breast.

Mutations in the p53 tumor suppressor gene are frequent in breast tumors but the implication of p53 mutations in breast cancer development remains poorly understood. In this study, we applied laser capture microdissection (LCM) microscope to histologically review and sample cells from paraffin-embedded breast tissue sections obtained from six cases of ductal carcinoma in situ (DCIS) and ten cases of atypical ductal hyperplasia (ADH). p53 mutations were detected, using single stranded conformational polymorphism (SSCP) and sequencing, in cell samples of three cases with DCIS and five cases with ADH. p53 mutations are therefore present in DCIS and ADH of the breast, considered as pre-malignant precursors to breast cancer, and some of them may represent early events in breast cancer development.

Morphologic features do not influence response to trastuzumab-containing neoadjuvant chemotherapy in HER2-positive breast cancer.

Trastuzumab-containing neoadjuvant chemotherapy in patients with HER2-positive breast cancer is highly effective in reducing tumor volume and enables more patients to have breast-conserving surgery. The tumor hormone receptor level has been shown to significantly influence response to trastuzumab-containing neoadjuvant chemotherapy. In this study, we comprehensively evaluated various morphologic features and proliferative activity in 50 HER2-positive invasive breast carcinomas treated with trastuzumab-containing neoadjuvant chemotherapy to determine whether any of these features have the same predictive value as tumor hormone receptor content. The tumor proliferation activity as measured by Ki-67 and various morphologic parameters were compared between tumors that achieved >50% tumor volume reduction including pathologic complete response (pCR) and tumors that showed ≤50% tumor volume reduction. Thirty-seven cases (74%) showed >50% tumor volume reduction including 18 cases with pCR. Thirteen cases (26%) showed ≤50% tumor volume reduction. Neither morphologic variables nor Ki-67 labeling index were predictive of >50% tumor volume reduction. In contrast, hormone receptor status and semiquantitative H scores for hormone receptors were predictive of>50% tumor volume reduction. The mean estrogen and progesterone receptor H scores for tumors that showed >50% tumor volume reduction (including pCR) were 77 (median 10) and 31 (median 0), respectively, compared with 168 (median 200) and 79 (median 75) for cases that showed ≤50% tumor volume reduction. Semiquantitative scoring for hormone receptors provides useful information in terms of therapeutic response in HER2-positive tumors.

Cytology and human papillomavirus screening test results associated with 2827 histopathologic diagnoses of cervical intraepithelial neoplasia 2/3.

CONTEXT: Cervical screening in the United States increasingly involves newer US Food and Drug Administration-approved cytologic methods and adjunctive high-risk human papillomavirus (hrHPV) DNA testing. OBJECTIVE: To document cervical screening test performance preceding histopathologic cervical intraepithelial neoplasia (CIN) 2/3 diagnoses. DESIGN: Preceding screening test results with computer-imaged, liquid-based cytology (LBC) and hrHPV results were analyzed for 2827 patients with histopathologic CIN 2/3 diagnoses. RESULTS: Of 2827 patients with CIN 2/3 diagnoses, 2074 (73.4%) had system LBC findings within 4 months of CIN 2/3 diagnoses: high-grade squamous intraepithelial lesion (n = 862; 41.6%), low-grade squamous intraepithelial lesion (n = 464; 22.4%), atypical squamous cells of undetermined significance (n = 445; 21.5%), atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (n = 288; 13.9%), and atypical glandular cells/adenocarcinoma in situ (n = 15; 0.7%). Of the 2827 patients, 1488 (52.6%) also had earlier system LBC results at more than 4 months to 3 years before CIN 2/3 diagnoses: one or more abnormal LBC results (n = 978; 65.7%), one or more negative LBC results (n = 911; 61.2%), both abnormal and negative LBC (n = 401; 26.9%). Of 807 patients with hrHPV cotest results within 4 months of CIN 2/3 diagnoses, 786 (97.4%) had hrHPV(+) results. Of 454 patients who also had earlier hrHPV results at more than 4 months to 3 years before CIN 2/3 diagnoses: 377 (83.0%) had one or more hrHPV(+) result, 110 (24.2%) had one or more hrHPV(-) result, and 33 (7.3%) had both positive and negative HPV results. CONCLUSION: Patients with histopathologic CIN 2/3 had recent abnormal LBC results, most often, high-grade squamous intraepithelial lesions. Among cotested patients, 97.4% (786 of 807) tested hrHPV(+). However, a significant number of patients tested during an extended period of several years had earlier negative Papanicolaou or negative HPV test results, suggesting the recent development of some CIN 2/3 lesions and supporting the value of cotesting for enhanced detection of other developing, small, inaccessible, or nondiagnostic precursor lesions.

Rationale of excisional biopsy after the diagnosis of benign radial scar on core biopsy: a single institutional outcome analysis.

BACKGROUND: Radial scar (RS) is characterized by a fibroelastic core with entrapped ducts and lobules. Association with carcinoma is not uncommon. There is some dilemma as to the need for excisional biopsy or follow-up after RS diagnosis on core biopsy. AIM: To determine the necessity of excisional biopsy after the diagnosis of benign RS by core biopsy. STUDY DESIGN: A total of 67 RS specimens associated with benign findings on core biopsy obtained between 2003 and 2008 were reviewed. They were grouped by their accompanying histopathologic features found upon subsequent surgical excision: benign, high-risk lesion (HRL), or carcinoma. Demographic features, radiologic findings, and needle gauge were compared within subgroups. RESULTS: After surgical excision, 15 (22.4%) patients in the benign group were upgraded to a HRL, 4 (5.9%) patients were upgraded to carcinoma, and 48 (71.6%) remained benign. We found that malignancy is associated with RS more frequently if the patient is older and postmenopausal. Other variables such as symptoms at presentation, presence and type of abnormality on mammography (Breast Imaging Reporting and Data System score), breast density, size of biopsy needle used, and number of core samples retrieved did not help to predict the presence of carcinoma. CONCLUSIONS: The HRL and cancer upgrade rate of RS, requiring further intervention such as surgery or chemoprevention, is 28% in this study. However, we found that age and menopausal status may be taken into consideration when making the decision to follow up or excise the RS diagnosed on core biopsy. There is insufficient data to support the predictive value of any variables. Therefore, RS associated with benign findings on core biopsy should be excised.