Shrinkage versus fragmentation response in neoadjuvantly treated oesophageal adenocarcinoma: significant prognostic relevance.

AIMS: No consensus exists on the clinical value of tumour regression grading (TRG) systems for therapy effects of neoadjuvant chemoradiotherapy (nCRT) in oesophageal adenocarcinoma. Existing TRG systems lack standardization and reproducibility, and do not consider the morphological heterogeneity of tumour response. Therefore, we aim to identify morphological tumour regression patterns of oesophageal adenocarcinoma after nCRT and their association with survival. METHODS AND RESULTS: Patients with oesophageal adenocarcinoma, who underwent nCRT followed by surgery and achieved a partial response to nCRT, were identified from two Dutch upper-gastrointestinal (GI) centres (2005-18; test cohort). Resection specimens were scored for regression patterns by two independent observers according to a pre-defined three-step flowchart. The results were validated in an external cohort (2001-17). In total, 110 patients were included in the test cohort and 115 in the validation cohort. In the test cohort, two major regression patterns were identified: fragmentation (60%) and shrinkage (40%), with an excellent interobserver agreement (κ = 0.87). Here, patients with a fragmented pattern had a significantly higher pathological stage (stages III/IV: 52 versus 16%; P < 0.001), less downstaging (48 versus 91%; P < 0.001), a higher risk of recurrence [risk ratio (RR) = 2.9, 95% confidence interval (CI) = 1.5-5.6] and poorer 5-year overall survival (30 versus 80% respectively, P = 0.001). CONCLUSIONS: The validation cohort confirmed these findings, although had more advanced cases (case-stages = III/IV 91 versus 73%, P = 0.005) and a higher prevalence of fragmented-pattern cases (80 versus 60%, P = 0.002). When combining the cohorts in multivariate analysis, the pattern of response was an independent prognostic factor [hazard ratio (HR) = 1.76, 95% CI = 1.0-3.0]. In conclusion, we established an externally validated, reproducible and clinically relevant classification of tumour response.

Histological subtypes in triple negative breast cancer are associated with specific information on survival.

Much research has focused on finding novel prognostic biomarkers for triple negative breast cancer (TNBC), whereas only scattered information about the relation between histopathological features and survival in TNBC is available. This study aims to explore the prognostic value of histological subtypes in TNBC. A multicenter retrospective TNBC cohort was established from five Dutch hospitals. All non-neoadjuvantly treated, stage I-III patients with estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 negative breast cancer diagnosed between 2006 and 2014 were included. Clinical and follow-up data (overall survival; OS, relapse free survival; RFS) were retrieved and a central histopathological review was performed. Of 597 patients included (median follow up 62.8 months, median age at diagnosis 56.0 years), 19.4% developed a recurrence. The most prevalent histological subtypes were carcinoma of no special type (NST) (88.4%), metaplastic carcinoma (4.4%) and lobular carcinoma (3.4%). Collectively, tumors of special type were associated with a worse RFS and OS compared to carcinoma NST (RFS HR 1.89; 95% CI 1.18-3.03; p = 0.008; OS HR 1.94; 95% CI 1.28-2.92; p = 0.002). Substantial differences in survival, however, were present between the different histological subtypes. In the presented TNBC cohort, special histological subtype was in general associated with less favorable survival. However, within the group of tumors of special type there were differences in survival between the different subtypes. Accurate histological examination can provide specific prognostic information that may potentially enable more personalized treatment and surveillance regimes for TNBC patients.

Does Nipple Discharge Color Predict (pre-) Malignant Breast Pathology?

Unilateral single-duct nipple discharge is associated with an increased risk for underlying breast malignancy. There is no consensus whether color of nipple discharge independently indicates the risk of malignancy. We sought to assess the relationship between the color of discharge and the risk of malignancy. Patients with unilateral single-duct nipple discharge without abnormalities on clinical and radiologic examination were included. Prior to diagnostic microdochectomy nipple discharge characteristics were registered. Multiple logistic regressions were performed to assess the relationship between color of nipple discharge and malignancy, corrected for age. During a mean follow-up period of 7.1 years we determined complication rate and false-negative rate of microdochectomy. A total of 184 patients were included (median age 53 years, range 19-84). Histologic examination revealed (in situ or invasive) breast carcinoma in 10.9% (20) of patients and high-risk lesions in 11.4% (21). Malignancy or high-risk lesions were found in 25% (OR: 1.37; 95% CI: 0.62-3.00) of patients with bloody discharge. Risk of underlying malignancy increased in patients >60 years (OR: 2.35; 95% CI: 1.14-4.83). Complication rate of microdochectomy was 2.7%. Single-duct, unilateral nipple discharge is a sign of underlying malignancy in a substantial proportion of cases. The majority of patients with unilateral single-duct nipple discharge, diagnosed with breast cancer, present with bloody discharge. However, the association between bloody nipple discharge and malignancy is not strong enough to distinguish high-risk patients. Therefore, invasive diagnostic procedures like microdochectomy should be offered to all patients with unilateral uniductal nipple discharge to search for underlying malignancy.

USPIO-enhanced MRI of lymph nodes in rectal cancer: A node-to-node comparison with histopathology.

PURPOSE: To evaluate the initial results of predicting lymph node metastasis in rectal cancer patients detected in-vivo with USPIO-enhanced MRI at 3 T compared on a node-to-node basis with histopathology. METHODS: Ten rectal cancer patients of all clinical stages were prospectively included for an in-vivo 0.85 mm3 isotropic 3D MRI after infusion of Ferumoxtran-10. The surgical specimens were examined ex-vivo with an 0.29 mm3 isotropic MRI examination. Two radiologists evaluated in-vivo MR images with a classification scheme to predict lymph node status. Ex-vivo MRI was used for MR-guided pathology and served as a key link between in-vivo MRI and final histopathology for the node-to-node analysis. RESULTS: 138 lymph nodes were detected by reader 1 and 255 by reader 2 (p = 0.005) on in-vivo MRI with a median size of 2.6 and 2.4 mm, respectively. Lymph nodes were classified with substantial inter-reader agreement (κ = 0.73). Node-to-node comparison was possible for 55 lymph nodes (median size 3.2 mm; range 1.2-12.3), of which 6 were metastatic on pathology. Low true-positive rates (3/26, 11 % for both readers) and high true negative rates were achieved (14/17, 82 %; 19/22, 86 %). Pathological re-evaluations of 20 lymph nodes with high signal intensity on USPIO-enhanced MRI without lymph node metastases (false positives) did not reveal tumor metastasis but showed benign lymph node tissue with reactive follicles. CONCLUSIONS: High resolution MRI visualizes a large number of mesorectal lymph nodes. USPIO-enhanced MRI was not accurate for characterizing small benign versus small tumoral lymph nodes in rectal cancer patients. Suspicious nodes on in-vivo MRI occur as inflammatory as well as metastatic nodes.

Is cytology useful in the diagnostic workup of male breast lesions? A retrospective study over a 16-year period and review of the recent literature.

OBJECTIVE: To determine the value of cytology in the workup of male breast lesions, important for the management in a same-day breast clinic. STUDY DESIGN: A total of 146 fine needle aspirations (FNAs) from the male breast were classified in the categories malignant, suspicious, atypical, benign and inadequate. Cytohistologic correlation was done. RESULTS: Histologic correlation was available in 85 cases. On FNA the 15 malignant cases were classified as malignant (n = 11), suspicious for malignancy (n = 2) or atypical (n = 2). Of the 35 benign lesions on histology 3 cases were classified as atypia and 1 as suspicious for malignancy on FNA. In the inadequate FNAs (n = 45), the corresponding histologic specimens were benign, no carcinomas were diagnosed. The sensitivity and specificity of the FNA compared to the definite resection diagnosis were 100% and 90.2%, respectively. The results were comparable with the outcomes of the reviewed studies on male breast lesions in the recent literature. CONCLUSION: Based on the nature of the benign breast lesions in man, a substantial number of inadequate FNAs were obtained. However, due to the good cytohistologic correlations in the group of malignant lesions, we can conclude that cytology remains an important diagnostic tool in the initial workup of male breast carcinomas.

Brain metastasis from prostate small cell carcinoma: not to be neglected.

BACKGROUND: Symptomatic brain metastases from prostatic carcinoma are rare (0.05% to 0.5%). CASE REPORT: A 70-year-old man presented with a homonymous hemianopsia due to brain metastatic prostatic carcinoma shortly before becoming symptomatic of prostatic disease. CT and MRI of the brain showed a tumour deep in the right hemisphere near the thalamus and involving the optic radiation. RESULTS: Routine haematological and biochemical tests were normal. The prostate specific antigen level was low on two separate occasions. The prostatic and brain tumours showed identical appearances, namely of a poorly differentiated adenocarcinoma with neuroendocrine differentiation (small cell carcinoma). CONCLUSION: A literature review suggests that small cell carcinoma of the prostate is more likely to spread to the brain compared to adenocarcinoma and that brain metastases indicate a poor prognosis. The prostate gland should be remembered as a possible cause of brain metastases and that a normal serum prostate specific antigen does not exclude this diagnosis.

More tumor-affected lymph nodes because of the sentinel lymph node procedure but no stage migration, because the 2002 TNM classifies small tumor deposits as pathologic N0 breast cancer.

BACKGROUND: Intensified examination of the sentinel lymph node (SN) may result in increased detection of tumor-affected lymph nodes. The authors of this report hypothesized that the introduction of the SN procedure has led to stage migration because of the intensified workup of SNs by pathologists. METHODS: After the introduction of the SN procedure, 360 patients with operable breast cancer were included prospectively from 2 large hospitals (Hospital A and Hospital B). The prospectively included patients (the "SN era" group) were compared with 88 historic controls from the year 1994 who were diagnosed with primary breast cancer before introduction of the SN procedure. RESULTS: After correcting for classic clinical and pathologic prognostic factors in a multiple logistic regression analysis, the detection frequency of lymph node involvement was significantly higher in the SN era group compared with historic controls (P = .04). However, when using the 2002 TNM classification, in which isolated tumor cells (