Lymphoepithelioma-like carcinoma of the breast: cytological and histological features and review of the literature.

OBJECTIVE: We present, for the first time, the cytological features of lymphoepithelioma-like carcinoma (LELC) of the breast in preoperative fine-needle aspiration (FNA) and touch imprints from secondary deposits in the sentinel lymph node (SLN). STUDY DESIGN: We report a case of a 53-year-old woman who was diagnosed with breast carcinoma on preoperative FNA and was subjected to SLN biopsy, partial mastectomy and axillary lymph node dissection. The final diagnosis was LELC of the breast. Cytological and histological features were analyzed. RESULTS: The smears from preoperative FNA contained cohesive clusters and isolated tumour cells in a haemorrhagic background with scattered lymphocytes. Some of the clusters were infiltrated by the inflammatory cells. The cells had large, pleomorphic nuclei and scanty, ill-defined cytoplasm. The intraoperative touch imprints from the SLN were highly cellular, comprising abundant scattered lymphoid cells, among which were tight clusters of indistinct cells, about 3 times larger than the lymphocyte population. CONCLUSION: In our case, LELC shares many cytological features with LELC described in other organs. Immunostains with epithelial markers play an important role in establishing the epithelial nature of the neoplastic cells. LELC should be borne in mind in the evaluation of breast lesions with prominent lymphoid cell infiltration. Its cytological features, as presented, could contribute to its preoperative evaluation on cytological grounds.

Discordant expression of hormone receptors and HER2 in breast cancer. A retrospective comparison of primary tumors with paired metachronous recurrences or metastases.

PURPOSE: Expression of biomarkers in breast cancer, such as the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), can impact therapeutic decisions; however, it has been reported that their expression may change with disease progression. The aim of this retrospective study was to investigate the expression of these biomarkers in primary breast cancer and in its metachronous recurrences or metastases, and to estimate the percentage of cases with discordant expression. METHODS: Paired primary and metastatic tumor samples were collected from patients with primary breast cancer and subsequent metachronous distant metastases, diagnosed at the Metaxa Cancer Hospital, Piraeus, Greece, from 1988 to 2008. Two cases of local recurrence were also included. ER, PR and HER2 expression were assessed by immunohistochemistry (IHC) according to ASCO-CAP 2007 guidelines. Statistical comparisons were made using McNemar's exact test and Bowker's test for symmetry. RESULTS: Tumor samples from 110 patients were analysed. In the primary tumor, ER, PR and HER2 were positively expressed in 64.5%, 58.2% and 32.7% of cases, respectively, and expression of these biomarkers was lost in 18.2%, 21.8% and 10.9% of the corresponding metastases, respectively. Overall, a change of ER, PR and HER2 expression from positive to negative and vice versa occurred in 27.3% (p = 0.0987), 25.5% (p < 0.001) and 18.2% (p = 0.5034) of the cases, respectively. CONCLUSION: The expression of ER, PR and HER2 in metachronous recurrences or metastases can be discordant from that observed in the primary tumor. As such changes can occur during disease progression, the evaluation of biomarkers in metastatic sites should be mandatory, whenever possible, to ensure that patients are receiving the most effective treatment at all times.

Prognostic importance of thymidylate synthase expression in early breast cancer.

PURPOSE: To assess the prognostic importance of thymidylate synthase (TS) expression in breast tumors of patients with early-stage breast cancer, and to determine whether the benefit of chemotherapy (CT) is associated with TS expression. PATIENTS AND METHODS: The level of TS expression was evaluated in 210 node-negative and 278 node-positive patients enrolled onto Trial V of the International Breast Cancer Study Group ([IBCSG] formerly the Ludwig Breast Cancer Study Group) with a median follow-up time of 8.5 years. TS expression was assessed using the immunohistochemical method with the monoclonal antibody TS 106 on paraffin-embedded tissue specimens. RESULTS: High TS expression was associated with a significantly worse prognosis in node-positive but not in node-negative breast cancer patients. Twenty-seven percent of node-positive patients with high TS expression were disease-free at 10 years, compared with 44% of node-positive patients with low TS expression (P = .03). Forty-one percent of patients with node-positive high-TS-expressing tumors were alive after 10 years, compared with 49% of those with low TS expression (P = .06). The association between TS and disease-free survival (DFS) and overall survival (OS) was independent of other prognostic factors such as tumor size, tumor grade, nodal status, vessel invasion, estrogen receptor (ER)/ progestin receptor (PR) status, c-erb B-2, or Ki-67 expression. In node-positive patients, six cycles of standard adjuvant cyclophosphamide, methotrexate, and fluorouracil ([5-FU] CMF) CT improved DFS and OS compared with one cycle of perioperative CMF therapy. The magnitude of this benefit was greatest in patients whose tumors had high TS expression (P < .01 for DFS; P < .01 for OS). Node-negative patients demonstrated no difference in outcome to CT based on TS expression; however, the power to detect differences was limited by the small number of events in this group. CONCLUSION: In early-stage breast cancer, high TS expression is associated with a significantly worse prognosis in node-positive patients. Node-positive patients with high TS levels demonstrate the most significant improvement in DFS and OS when treated with six cycles of conventional adjuvant CMF therapy.

Angiogenesis in ductal breast carcinoma. Comparison of microvessel density between primary tumour and lymph node metastasis.

Angiogenesis has been recognised as an important prognostic factor in cancer. This study assessed immunohistochemically (JC70 MoAb) the microvessel score (MS; in x 250 fields) in 35 breast ductal carcinomas with lymph node involvement. Sections from both primary tumours and invaded nodes were assessed. A significantly lower MS was observed in the metastatic foci (24.6 +/- 9 vs. 13.6 +/- 6; P < 0.0001) than in the primary lesions. However, linear regression analysis showed a significant direct correlation between the MS assessed in primary lesions and the related metastatic foci in the lymph nodes (P = 0.006, r = 045). The primary tumour to node (T/N) ratio was assessed; 11/35 cases had a node MS close to the score of the primary (T/N < 2), whilst 17/35 had a T/N ratio ranging from 3 to 7. Extracapsular node involvement was more frequent in cases with low T/N ratio. Angiogenesis in the metastatic foci was independent of the amount of growing stroma within the metastasis. Vessel density in the normal lymph nodes did not correlate with the MS within the node metastases. We conclude that cancer cells migrating to the nodes may have similar angiogenic abilities to the parental cells of the primary tumour. However, environmental factors probably related to node immune reaction against the invading tumour could be responsible for the reduced angiogenicity in the nodes. Further studies are required to investigate the suggested angiogenesis suppressing immune mechanisms occurring in the invaded lymph nodes of breast cancer patients and possible clinical implications.

Mixed ovarian neoplasm composed of struma ovarii and Brenner tumour. Report of a case.

The case is reported of a patient with a mixed lesion composed of struma ovarii and Brenner tumour. This is an extremely rare tumour and only two well documented cases were found in the English literature.

Solitary fibrous tumor of the pleura: a review.

Solitary fibrous tumor (SFT) of the pleura is a rare neoplasm that arises most commonly within the visceral pleura but may evolve from the parietal pleura of the chest, mediastinum or diaphragm. These tumors are most commonly diagnosed in the 6th to 7th decade of life with equal rates of occurrence for both sexes. In this review we discuss the clinical, radiographic and histological features, the diagnosis and differential diagnosis, prognostic factors and therapy of these rare tumors.

Microinvasive cervical carcinoma: a retrospective study of cases presenting to the Oxford Colposcopy Unit between 1989 and 1996.

This a retrospective analysis of 65 cases of microinvasive disease and 5-8 years of follow-up (mean 6.2 years), evaluating the effectiveness of cytology and colposcopy in the diagnosis of microinvasive disease and the role of conservative surgery in its management. Cervical cytology reports indicated disease more severe than CIN III in 23% of cases. A further 7% at colposcopy were thought to have possible invasive disease despite no indication from the smear report, this impression correlated with increasing depth of invasion (>1.40 mm).

The importance of the histologic grade of invasive breast carcinoma and response to chemotherapy.

BACKGROUND: Histologic grade is well recognized for its prognostic significance in cases of primary operable invasive breast carcinoma; however, the majority of studies in which grade has been assessed have been based on single-center trials. In addition, the role of grade in predicting response to chemotherapy has not been examined in many previous studies. METHODS: The authors assessed the value of Nottingham histologic grade (NHG) in a group of 465 patients enrolled in a multicenter, randomized International Breast Cancer Study Group clinical trial of adjuvant chemotherapy for patients with lymph node (LN) positive and LN negative primary breast carcinoma (formerly named Ludwig Trial V). RESULTS: NHG was a predictor of overall survival for both LN negative and LN positive patients (P=0.045 and P < 0.001, respectively). NHG was associated with a poorer prognosis for both LN positive and LN negative patients, with hazard ratios of 1.651 (P < 0.001) and 1.437 (P=0.045), respectively, for an increase of one grade. Among LN negative patients, this survival disadvantage was observed only for those who received perioperative chemotherapy. For LN positive patients, an increase of one grade resulted in a significant overall survival disadvantage regardless of whether prolonged or perioperative chemotherapy was given. For LN negative patients grouped by grade, there was no observed difference in overall or disease free survival according to whether perioperative chemotherapy or no adjuvant therapy was given. However, LN positive patients with Grade 3 tumors had a significantly greater overall and disease free survival benefit from prolonged chemotherapy than from perioperative chemotherapy (P=0.016 and P=0.013, respectively); LN positive patients with Grade 1 or 2 disease in both treatment arms had comparable overall and disease free survival. A strong correlation between the previously utilized Bloom-Richardson grading system (BRG) and NHG was observed (P < 0.001 and kappa=82%) and no apparent differences in overall and disease free survival were observed between the two systems. NHG did, however, identify a greater proportion of tumors as Grade 1, and BRG identified a greater proportion of breast carcinomas as Grade 3. CONCLUSIONS: This multicenter clinical study confirms the value of histologic grade, and the authors propose that this technique be used to identify Grade 3, LN positive patients who will benefit from prolonged rather than perioperative chemotherapy.