Age, PS, LDH serum level, CSF protein concentration, and involvement of deep structures of the brain were independent predictors of survival. A prognostic score including these five parameters seems advisable in distinguishing different risk groups in PCNSL patients. The proposed score and its relevance in therapeutic decision deserve to be validated in further studies.

Sentinel lymph node biopsy using a gamma ray-detecting probe allows staging of the axilla with high accuracy in patients with primary breast cancer. A randomized trial is necessary to determine whether axillary dissection may be avoided in those patients with an uninvolved sentinel lymph node.

Breast cancer encompasses a collection of different diseases characterized by different biological and pathological features, clinical presentation, response to treatments, clinical behavior, and outcome. On the basis of cell morphology, growth, and architecture patterns, breast cancer can be classified in up to 21 distinct histological types. Breast cancer special types, including the classic lobular invasive carcinoma, represent 25% of all breast cancers. The histological diversity of breast carcinomas has relevant prognostic implications. Indeed, the rare breast cancer group includes subtypes with very different prognoses, ranging from the tubular carcinoma, associated with an indolent clinical course, to metaplastic cancer, whose outcome is generally unfavorable. New approaches based on gene expression profiling allow the identification of molecularly defined breast cancer classes, with distinct biological features and clinical behavior. In clinical practice, immunohistochemical classification based on the expression of human epidermal growth factor receptor 2 and Ki67 is applied as a surrogate of the intrinsic molecular subtypes. However, the identification of intrinsic molecular subtypes were almost completely limited to the study of ductal invasive breast cancer. Moreover, some goodprognosis triple-negative histotypes, on the basis of gene expression profiling, can be classified among the poorprognosis group. Therefore, histopathological classification remains a crucial component of breast cancer diagnosis. Special histologies can be very rare, and the majority of information on outcome and treatments derives from small series and case reports. As a consequence, clear recommendations about clinical management are still lacking. In this review, we summarize current knowledge about rare breast cancer histologies. The Oncologist 2014;19:805-813 Implications for Practice: Breast cancer special histologies encompass a panel of various entities with peculiar clinical behaviors. The rarity of such histotypes has jeopardized an extensive clinical evaluation. A review of current available data may help physicians in their clinical practice; however, the development of clear clinical recommendations is not possible. Decisions on the management of patients with rare breast cancer histologies should derive from careful case-by-case multidisciplinary evaluations.

Invasive lobular carcinoma (ILC) is the most common "special type" of breast cancer. Although conflicting literature data are available on the outcome of ILC, recently reported data indicate that ILC carries a poorer prognosis if compared to invasive ductal carcinomas. We evaluated clinical and biological features of 981 consecutive patients with pT1-3, pN1-3 M0 ILC. Median follow-up was 7.4 years for survival. A total of 541 patients were classified as classic (55.8%), 146 alveolar (14.9%), 145 mixed non-classic (14.8%), 104 solid (10.6%), and 38 trabecular (3.9%). A statistically significant difference in the outcome was observed at multivariate analysis for patients with solid (HR 2.44, 95% CI 1.39-4.29 for OS; HR 1.92, 95% CI 1.29-2.88 for DFS) and mixed non-classic (HR 1.99, 95% CI 1.12-3.53 for OS) versus patients with classical ILC. A statistically significant difference in the risk of distant metastases was observed at multivariate analysis for patients with Luminal B (HR 2.56, 95% CI 1.38-4.76), HER2 positive (HR 7.80, 95% CI 1.55-39.3), and triple negative (HR 7.61, 95% CI 2.63-22.1) subtypes versus patients with Luminal A ILC. Age ≥70 years, tumor size and degree of nodal involvement were additional independent predictors of reduced overall survival. The outcome of ILC significantly correlated with histological and immunohistochemically defined molecular subtypes. New tailored strategies should be explored in these subgroups of patients with poor outcome.

The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC.