Discriminant analysis and machine learning approach for evaluating and improving the performance of immunohistochemical algorithms for COO classification of DLBCL.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is classified into germinal center-like (GCB) and non-germinal center-like (non-GCB) cell-of-origin groups, entities driven by different oncogenic pathways with different clinical outcomes. DLBCL classification by immunohistochemistry (IHC)-based decision tree algorithms is a simpler reported technique than gene expression profiling (GEP). There is a significant discrepancy between IHC-decision tree algorithms when they are compared to GEP. METHODS: To address these inconsistencies, we applied the machine learning approach considering the same combinations of antibodies as in IHC-decision tree algorithms. Immunohistochemistry data from a public DLBCL database was used to perform comparisons among IHC-decision tree algorithms, and the machine learning structures based on Bayesian, Bayesian simple, Naïve Bayesian, artificial neural networks, and support vector machine to show the best diagnostic model. We implemented the linear discriminant analysis over the complete database, detecting a higher influence of BCL6 antibody for GCB classification and MUM1 for non-GCB classification. RESULTS: The classifier with the highest metrics was the four antibody-based Perfecto-Villela (PV) algorithm with 0.94 accuracy, 0.93 specificity, and 0.95 sensitivity, with a perfect agreement with GEP (κ = 0.88, P < 0.001). After training, a sample of 49 Mexican-mestizo DLBCL patient data was classified by COO for the first time in a testing trial. CONCLUSIONS: Harnessing all the available immunohistochemical data without reliance on the order of examination or cut-off value, we conclude that our PV machine learning algorithm outperforms Hans and other IHC-decision tree algorithms currently in use and represents an affordable and time-saving alternative for DLBCL cell-of-origin identification.

[Mixed adenoneuroendocrine carcinoma: case report]. / Carcinoma adenoneuroendocrino mixto: reporte de caso.

Introducción: Mixed adenoneuroendocrine carcinoma is a rare tumor of the gastrointestinal tract with double differentiation into adenomatous and neuroendocrine carcinoma, each component with at least 30%. Case report: A 60-year-old female with acute abdominal pain. Surgical treatment was decided, finding a tumor at the level of the cecum and ascending colon, a right hemicolectomy and ileostomy were performed. Discussion: Mixed adenoneuroendocrine carcinoma can appear in various organs. They are highly malignant tumors, with a high risk of metastasis. Conclusions: These tumors do not present symptoms or specific radiological or laboratory findings; diagnosis depends on postoperative histopathological and immunohistochemical studies.

Introducción: El carcinoma adenoneuroendocrino mixto es un tumor raro del tracto gastrointestinal con doble diferenciación en carcinoma adenomatoso y neuroendocrino, cada componente con al menos el 30%. Caso clínico: Mujer de 60 años con cuadro de dolor abdominal agudo. Se decide tratamiento quirúrgico, encontrando un tumor a nivel de ciego y colon ascendente, y se realizan hemicolectomía derecha e ileostomía. Discusión: El carcinoma adenoneuroendocrino mixto puede aparecer en diversos órganos. Son tumores muy malignos, con alto riesgo de metástasis. Conclusiones: Estos tumores no presentan síntomas ni hallazgos radiológicos o de laboratorio específicos; el diagnóstico depende de estudios histopatológicos e inmunohistoquímicos posoperatorios.

Unusual morphologic presentations of blastic plasmacytoid dendritic cell neoplasm: report of two cases misdiagnosed as melanoma and leprosy.

We present 2 cases of blastic plasmacytoid dendritic cell neoplasm (BPDCN) showing unusual histological features. One patient, a 73-year-old male, presented with a nonpruritic macular erythema of the skin on the anterior and posterior chest wall, the biopsy of which was originally diagnosed as malignant melanoma. The neoplastic cells were negative for S100 and HMB45 and strongly positive for CD45, CD4, CD56, and CD123. The final diagnosis was a BPDCN associated with abundant melanin pigment and numerous melanophages. The second patient was a 73-year-old male with a 5-month history of small, slowly enlarging, bruise-like plaques on his limbs and chest. Histologic examination of the skin biopsy revealed an atypical cellular/myxoid infiltrate with numerous macrophages, which was originally diagnosed as consistent with lepromatous leprosy. The atypical cells were immersed in an alcian blue-positive myxoid matrix at pH 2.5. The Fite-Faraco stain was negative. Positive immunoreactivity was demonstrated for CD4, CD56, and CD123. Based on the histopathology and immunohistochemistry findings, a diagnosis of BPDCN with prominent myxoid matrix was rendered.