The human epidermal growth factor receptor 2 (HER2) is a well-known negative prognostic factor in breast cancer and a target of the monoclonal antibody trastuzumab as well as of other anti-HER2 compounds. Pioneering works on HER2-positive breast cancer in the 90s' launched a new era in clinical research and oncology practice that has reshaped the natural history of this disease. In diagnostic pathology the HER2 status is routinely assessed by using a combination of immunohistochemistry (IHC, to evaluate HER2 protein expression levels) and in situ hybridization (ISH, to assess HER2 gene status). For this purpose, international recommendations have been developed by a consensus of experts in the field, which have changed over the years according to new experimental and clinical data. In this review article we will document the changes that have contributed to a better evaluation of the HER2 status in clinical practice, furthermore we will discuss HER2 heterogeneity defined by IHC and ISH as well as by transcriptomic analysis and we will critically describe the complexity of HER2 equivocal results. Finally, we will introduce the clinical impact of HER2 mutations and we will define the upcoming category of HER2-low breast cancer with respect to emerging clinical data on the efficacy of specific anti-HER2 agents in subgroups of breast carcinomas lacking the classical oncogene addition dictated by HER2 amplification.

Colonic intussusception is a rare cause of intestinal obstruction in adults and is caused by a malignant lesion in about 70% of cases. Early diagnosis and treatment are essential. We present a 64-year-old male patient with right colonic intussusception caused by a mixed adenoneuroendocrine carcinoma (MANEC), presenting as a giant pedunculated polyp (54 mm of largest diameter). The patient underwent right colectomy with primary anastomosis and adjuvant chemotherapy. The diagnosis of intussusception of the colon in adults is difficult because of its rarity and nonspecific clinical presentation. In this case, the cause was a rare histological type malignant tumor (MANEC).

Background: Molecular profiling in upper tract urothelial carcinoma (UTUC) with synchronous or metachronous urothelial bladder cancer (UBC) is scarce. We intended to assess immunohistochemical (IHC) and genetic differences between UTUC-only and UTUC with synchronous or metachronous UBC (UTUC + UBC) and evaluate the effect of subsequent UBC on the outcome of UTUC patients stratified by luminal-basal subtypes. Methods: A retrospective cohort of UTUC was divided into UTUC-only (n = 71) and UTUC + UBC (n = 43). IHC expression of cytokeratin 5/6 (CK5/6), CK20, GATA3, and p53 was evaluated to assess relevant subtypes. Genetic characterization comprised TERTp, FGFR3, RAS, and TP53 status. Kaplan–Meier and Cox regression analyses estimated the effect of clinicopathological variables and molecular profiles on progression-free survival (PFS) and overall survival (OS) of UTUC patients. Results: No meaningful differences were detected among both subgroups according to luminal-basal stratification and genetic analysis. UTUC + UBC was independently associated with a worse PFS when stratified by luminal-basal phenotype (HR 3.570, CI 95% 1.508–8.453, p = 0.004) but with no impact in OS (HR 1.279, CI 95% 0.513–3.190, p = 0.597). Conclusions: This study reveals that both subgroups exhibited equivalent genomic features and luminal-basal subtypes. The involvement of the bladder relates to shorter PFS but does not seem to influence the survival outcome of UTUC, independently of the IHC phenotype.

Cutaneous metastases from squamous cell carcinomas of the head and neck region are uncommon, and their location at the nasal tip is exceptionally rare. A patient, previously treated with surgery and chemoradiation for a hypopharyngeal squamous cell carcinoma, developed several red nodular skin lesions at the nasal tip. Biopsy revealed cutaneous metastasis from the primary tumor. This manifestation was previously described as a “clown nose,” given their appearance and location. Skin lesions should raise suspicion of malignancy, despite their location at uncommon places, particularly in patients with previous diagnosed cancer. Clinicians must be aware that metastases from head and neck cancer can present as a “clown nose.”

Heterotopia gástrica · Estenose · Impactação alimentar ·