ABSTRACT
BACKGROUND: Rosai-Dorfman disease (RDD), a rare form of non-Langerhans cell histiocytosis with heterogenous clinical features, arises from precursor cells that give rise to cells of the histiocytic and monocytic lineages. An association with hematological neoplasms has been reported. Testicular RDD is rarely described, with only 9 reported cases in the literature. Genetic data to assess clonal relationships between RDD and other hematological neoplasms remain scarce. We describe an instance of testicular RDD against a background of chronic myelomonocytic leukemia (CMML), with genetic studies in both neoplasms. CASE PRESENTATION: A 72-year-old patient with a history of CMML sought evaluation of growing bilateral testicular nodules. Solitary testicular lymphoma was suspected; orchidectomy was performed. The diagnosis of testicular RDD was established morphologically and confirmed immunohistochemically. Molecular analysis of testicular lesions and of archived patient bone marrow revealed the KRAS variant c 0.35 G>A / p.G12D in both, suggesting a clonal relationship. CONCLUSION: These observations support classifying RDD as a neoplasm that can be clonally related to myeloid neoplasms.
Subject(s)
Histiocytosis, Sinus , Leukemia, Myelomonocytic, Chronic , Lymphoma, Non-Hodgkin , Male , Humans , Adult , Aged , Histiocytosis, Sinus/genetics , Histiocytosis, Sinus/complications , Histiocytosis, Sinus/diagnosis , Leukemia, Myelomonocytic, Chronic/genetics , Histiocytes/pathology , Bone Marrow/pathologyABSTRACT
Inter-test concordance between the MammaPrint and the EndoPredict tests used to predict the risk of recurrence in breast cancer was evaluated in 94 oestrogen receptor-positive, HER2-negative breast cancers. We correlated histopathological data with clinical risk estimation as defined in the MINDACT trial. 42.6% (40/94) of cases were high-risk by MammaPrint, 44.7% (42/94) by EndoPredict (EPclin), and 45.7% (43/94) by clinical risk definition. Thirty-six percent of genomic risk predictions were discordant with a low inter-test correlation between EndoPredict and MammaPrint (p = 0.012; κ = 0.27, 95% CI [0.069, 0.46]). Clinical risk stratification did not correlate with MammaPrint (p = 0.476) but highly correlated with EndoPredict (p < 0.001). Consequently, clinically high-risk tumours (n = 43) were more frequently high-risk by EndoPredict than by MammaPrint (76.6% vs. 46.5%, p = 0.004), with 44% of cases discordantly classified and no significant association between genomic risk predictions (p = 0.294). Clinicians need to be aware that clinical pre-stratification can profoundly influence multigenomic test performance.
Subject(s)
Breast Neoplasms/genetics , Breast Neoplasms/pathology , Gene Expression Profiling/methods , Genetic Testing/methods , Neoplasm Recurrence, Local/genetics , Female , Humans , Risk Assessment/methodsABSTRACT
INTRODUCTION: Correct risk assessment of disease recurrence in patients with early breast cancer is critically important to detect patients who may be spared adjuvant chemotherapy. In clinical practice this is increasingly done based on the results of gene expression assays. In the present study we compared the concordance of the 70-gene signature MammaPrint (MP) with the 12 gene assay EndoPredict (EP). METHODS: Representative tissue of 48 primary tumours was analysed with the MP during routine diagnostic purposes. Corresponding formalin-fixed, paraffin-embedded tissue was thereafter analysed by the EP test. Risk categories of both tests were compared. RESULTS: 41 of 48 tumours could be directly compared by both tests. Of the 17 MP low risk cases, only 9 were considered low risk by EP (53% agreement) and of the 24 MP high risk cases, 18 were high risk by EP (75% agreement). Discrepancies occurred in 14 of 41 cases (34.1%). There was only a weak and non-significant correlation between the MP and EP test with an overall concordance of only 66%. The original therapeutic recommendation was based on the MP and would have been changed in 38% of the patients following EP test results. 4 patients developed distant metastases. The respective tumours of these patients were all classified as high risk by the EP, but only 3 were classified as high risk by the MP. CONCLUSION: Both tests resulted in different treatment recommendations for a significant proportion of patients and cannot be used interchangeably. The results underscore the urgent need for further comparative analyses of multi-genomic tests to avoid misclassification of disease recurrence risk in breast cancer patients.
