Tumor Heterogeneity in Colorectal Cancer: What Do We Know So Far?

Colorectal cancer is not one disease but rather a collection of neoplastic diseases. Due to heterogeneity in the disease biology, therapy response, and prognosis, extensive disease stratification is required. Therefore, TNM stage, microsatellite status, tumor grade, lymphovascular invasion, and other parameters are assessed in the pathology report to indicate the extent and prognosis of the disease. The mutation status of KRAS, BRAF, and NRAS is also investigated in a metastatic context to predict the response to anti-EGFR therapy. Recently, 4 distinct molecular subtypes of colorectal cancer have been described that have both prognostic and therapeutic relevance. In addition, characterization of the inflammatory infiltrate revealed major differences in the amount and location of inflammatory cells in distinct colorectal tumor types. Together, all of these parameters help to stratify patients into different therapeutic and prognostic subgroups. However, this stratification is not unambiguous since tumors often display intratumoral heterogeneity, whereby several subpopulations within one tumor show differences in morphology, inflammatory infiltrate, mutational status, or gene expression profile. This article gives an overview of all of the current known data with regard to tumor heterogeneity at both inter- and intratumoral levels.

Case report: Cardiac intimal sarcoma in a young child.

Undifferentiated mesenchymal tumors from the intimal layer (intimal sarcomas) are rare within the ventricles and exceptional in children. A rare case of an intimal sarcoma located in the right ventricle in a young child is presented with need for urgent surgical resection due to mechanical flow obstruction. Tumor cells showed amplification of MDM2 gene and a homozygous loss of CDKN2A on 9p21. A review of the literature regarding primary cardiac malignancies and intimal sarcoma in children is provided.

Breast implant associated EBV-positive Diffuse Large B-cell lymphoma: an underrecognized entity?

Breast-implant associated (BIA) lymphoma is an infrequent type of cancer occurring in the fluid and fibrous capsule around a textured breast implant. Recently, both the 2022 WHO 5th edition classification of Haematological tumours (WHO HAEM5) and 2022 International Consensus Classification of Mature Lymphoid Neoplasms (22ICC), recognized breast implant-associated Anaplastic Large Cell Lymphoma (BIA-ALCL) as a definitive entity, defined as a mature CD30-positive T-cell lymphoma, confined by a fibrous capsule, in a breast implant setting. Only few B-cell lymphomas have been reported in the literature to be associated with breast implants. Here we report two EBV-positive Diffuse Large B-cell lymphomas (EBV + DLBCL) in relation to a breast implant, both expressing CD30 as well as EBV latency type 3. Both lesions were considered as DLBCL associated with chronic inflammation (CI-DLBCL), but one presented as a 7 cm solid mass, while the other presented as a fibrin-associated DLBCL (FA-DLBCL) in an HIV patient. Clinically, both are in complete remission 6 months or longer after capsulectomy and graft removal, without additional chemotherapy.Such cases, characterized by large CD30-positive cells, can easily be misdiagnosed as BIA-ALCL if the cell of origin is not further established. Therefore, a diagnostic panel including lineage-specific B-and T-cell markers and EBER in situ hybridization is essential to recognize this rare entity, to understand lymphomagenesis, to predict outcome and to define clinical approach.

Pembrolizumab-induced necrotizing myositis in a patient with metastatic non-small-cell lung cancer: a case report.

A 57-year-old man presented with swelling and pain in the lower limbs, inability to walk and increasing dyspnea for 2 days. Because of refractory stage IV non-small-cell lung cancer, pembrolizumab was started 21 days before presentation. Since then, he experienced general discomfort, fatigue and bilateral weakness in the legs with exercise limitation. A diagnosis of pembrolizumab-induced grade III myositis was made based on muscle biopsy. Pembrolizumab is a humanized monoclonal antibody against PD-1. It has been approved for the treatment of metastatic melanoma and refractory non-small-cell lung cancer with increased expression of PD-L1 on the cell surface of tumor cells. With such a humanized monoclonal antibody, fewer adverse events are expected than with systemic chemotherapy. However, 13% of patients develop autoimmune side effects which can be severe (grade III, IV or V) in 5-10%. We discuss a case of pembrolizumab-induced myositis, with a brief overview of the literature. Only three cases of pembrolizumab-induced myositis have been reported in literature.