Complete pathologic response rate to neoadjuvant chemotherapy increases with increasing HER2/CEP17 ratio in HER2 overexpressing breast cancer: analysis of the National Cancer Database (NCDB).

BACKGROUND: HER2-positive breast cancer is an aggressive subtype of breast cancer that overexpresses human epidermal growth factor receptor 2 promoting cancer cell growth. Monoclonal antibodies targeting the HER2 receptor have improved survival for this patient population. Achieving pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) has correlated with disease-free survival in multiple trials, but we do not know why some HER2-positive tumors respond better to these therapies. We evaluated the correlation between HER2/CEP17 ratio and partial versus complete response following NAC. We evaluated whether patients with higher HER2/CEP17 ratios would have higher rates of pCR after NAC. METHODS: Using the National Cancer Database (NCDB), we performed a retrospective review comparing pCR rates after NAC based on HER2 ratio between 2005 and 2014. Patients were excluded if they were HER2 negative, did not undergo NAC, or if the HER2 ratio was not recorded. Trends in percentage of pCR versus partial response were analyzed using SPSS. RESULTS: The NCDB included 237,118 patients with HER2 equivocal or HER2-positive breast tumors. 29,291 of these patients underwent NAC, and HER2/CEP17 ratios were recorded in 14,597 of the NAC cases. A pCR was noted in 9752 patients and 11,402 patients had a partial response. The ratios were significantly different between complete vs. partial response groups (include ratios), P < 0.001. Using linear regression analysis, we identified a direct relationship between increasing the ratio and response to NAC. CONCLUSION: Our study demonstrates a linear relationship between HER2/CEP17 ratio and pCR to NAC in patients included in the NCDB. The NCDB reflects current clinical practices across the country, and in this patient population, higher HER2 ratio is predictive of pCR to NAC and thus may be used in guiding decisions regarding the therapies that a patient receives in order to enhance pCR.

The role of fine needle aspiration cytology in the diagnosis and management of thymic neoplasia.

BACKGROUND: Fine needle aspiration biopsy is commonly used to document the metastasis to the mediastinum. It is less often used to make the primary diagnosis of tumors, particularly thymic neoplasms. This is due to fear of sampling error, rarity of thymic tumors, multiplicity of lesions in the mediastinum, and inexperience on the part of the cytopathologist. We show that needle aspiration sampling of thymic tumors, both thymoma and thymic carcinoma, is an accurate method of diagnosis. METHODS AND RESULTS: In our series of 22 thymic tumors aspirated preoperatively and compared with the subsequent surgical resection, the accuracy of a diagnosis of thymoma was 100%, and the accuracy of a diagnosis of carcinoma was 100%. Difficulties were encountered when vague terminology was used, and insufficient information was conveyed. Immunohistochemical stains can be applied to cytologic material to aid in the identification of the epithelial and lymphocytic components of thymoma. DISCUSSION: Correlation with clinical and radiographic information is necessary, and wording of the cytology report should be as complete and clear as possible.

Minimal disease in the sentinel lymph node: how to best measure sentinel node micrometastases to predict risk of additional non-sentinel lymph node disease.

BACKGROUND: Volume of disease in the sentinel lymph node (SLN) is a significant predictor of additional nodal metastasis. This study assesses incidence of residual non-SLN disease in a large cohort of women with minimal SLN metastases and compares three methods of SLN micrometastasis volume measurement to determine which best predicts residual disease on completion axillary lymph node dissection (cALND). METHODS: A total of 505 patients with invasive breast cancer and minimal SLN metastasis (pN1mi or pN0(i+)) underwent cALND and had complete data. All SLNs were evaluated by three measurement methods for volume of metastasis: (1) method of detection (frozen section, routine hematoxylin and eosin, serial hematoxylin and eosin, immunohistochemistry), (2) American Joint Committee on Cancer's AJCC Cancer Staging Manual, 7th edition, N category, and (3) number of metastatic cells (1-100, 101-999, ≥1000). Multivariable logistic regression models were used to predict the presence of additional non-SLN disease. RESULTS: A total of 251 patients (50%) had pN0(i+) and 254 patients (50%) had pN1mi disease. Twelve percent of those with pN0(i+) and 20% with pN1mi had additional non-SLN disease. On multivariate analyses including eight variables, only lymphovascular invasion (odds ratio >2.2, P < 0.01) and volume of nodal metastasis as assessed by any method of measurement (method of detection, AJCC, and cell count) were significantly correlated with additional non-SLN disease (P = 0.04, 0.03, and 0.02, respectively). All three models had similar goodness of fit and discrimination (Akaike information criterion = 442, 442, 441; -2log likelihood = 416, 420, 417; concordance index = 0.680, 0.675, 0.676, respectively). CONCLUSIONS: A significant proportion of women with minimal SLN metastases have additional non-SLN disease at cALND. Assessments of SLN volume of disease by three different methods of measurement are equivalent for prediction of additional non-SLN metastases.

Immunoprofile of adenocarcinomas of the endometrium, endocervix, and ovary with mucinous differentiation.

Primary mucinous tumors of the female genital tract have morphologic features similar to primary gastrointestinal adenocarcinomas, and distinguishing these malignancies may be extremely difficult. The purpose of this study was to characterize the immunostaining patterns of tumors of the female genital tract that show mucinous differentiation using cytokeratin 7 (CK7), CK20, and CDX2 and to evaluate the usefulness of these markers in differentiating these tumors from gastrointestinal tract adenocarcinomas and also from each other. A total of 64 cases were collected, including adenocarcinomas of the ovary (n=13), endocervix (n=16), endometrium (n=34), and vagina (n=1), all of which showed predominant mucinous differentiation. Intestinal mucinous differentiation was present in 11 of the cases (6 endocervical, 4 ovarian, and 1 vaginal adenocarcinoma). All tumors were at least focally positive for CK7 with the exception of 3 cases. The majority of tumors were negative for CK20 and CDX2. However, 25% of endocervical, 24% of ovarian, and 3% of endometrial adenocarcinomas were positive for CDX2, CK20, or both. The positivity for CDX2 and CK20 correlated with intestinal differentiation: 73% of all intestinal mucinous adenocarcinomas and 4% of all Müllerian mucinous adenocarcinomas showed positivity for the hindgut markers. In 70% of the tumors positive for CK20/CDX2, the intensity of CK7 stain was stronger than the intensity of either CK20 or CDX2 stain. In conclusion, immunostaining for CK7/CK20/CDX2 is helpful in distinguishing Müllerian subtype of mucinous gynecologic tumors from lower gastrointestinal tract malignancies. In gynecologic mucinous tumors with intestinal differentiation, the overlap of staining positivity may be a limiting factor. However, a dominant CK7 staining pattern was observed.

Overwhelming leukoencephalopathy as the only sign of neuropsychiatric lupus.

We describe a patient with diffuse leukoencephalopathy, a rare central nervous system complication of systemic lupus erythematosus, who died of brain herniation despite aggressive management. Brain magnetic resonance imaging revealed diffuse white matter hyperintensities consistent with vasogenic edema. Autopsy revealed only widespread cerebral edema. Early recognition and persistent, aggressive treatment will be required to avoid this fatal and rare manifestation of neuropsychiatric lupus.