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.
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.
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.
Das Kolorektalkarzinom ist keine einzelne Erkrankung, sondern umfasst vielmehr eine Gruppe von neoplastischen Erkrankungen. Aufgrund der Heterogenität der Erkrankung sowie des Therapieansprechens und der Prognose ist eine umfangreiche Stratifizierung der Krankheit erforderlich. Daher werden im Pathologiebericht TNM-Stadium, Mikrosatellitenstatus, Tumorgrad, Lymphgefäßeinbruch und andere Parameter bewertet, um das Ausmaß und die Prognose der Erkrankung aufzuzeigen. Ferner wird bei einer Metastasierung der KRAS-, BRAF- und NRAS-Mutationsstatus untersucht, um das Ansprechen auf eine Anti-EGFR-Therapie (EGFR = epidermaler Wachstumsfaktorrezeptor) vorherzusagen. Kürzlich wurden 4 unterschiedliche molekulare Subtypen des Kolorektalkarzinoms beschrieben, die sowohl von prognostischer als auch von therapeutischer Relevanz sind. Darüber hinaus zeigten sich in der Untersuchung des entzündlichen Infiltrats wesentliche Unterschiede hinsichtlich der Anzahl und Lokalisation der Entzündungszellen bei den verschiedenen Kolorektalkarzinomtypen. Die Gesamtheit dieser Parameter ermöglicht eine Stratifizierung der Patienten in verschiedene therapeutische und prognostische Subgruppen. Eine solche Stratifizierung ist jedoch nicht eindeutig, da Tumoren häufig intratumorale Heterogenität aufweisen, bei der verschiedene Subpopulationen innerhalb eines Tumors Unterschiede hinsichtlich Morphologie, entzündlichem Infiltrat, Mutationsstatus oder Genexpressionsprofil zeigen. Der vorliegende Artikel gibt einen Überblick über alle derzeit bekannten Daten zur Tumorheterogenität sowohl auf inter- als auch auf intratumoraler Ebene.
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