Sialadenoma papilliferum-like intraductal papillary tumor with unveiling BRAF V600E and PIK3CA H1047R mutations: Case report with molecular analysis and literature review.

INTRODUCTION: Sialadenoma papilliferum (SP), a rare minor salivary gland tumor, shares morphological and genetic similarities with syringocystadenoma papilliferum. Recent studies have identified BRAF V600E or HRAS mutations in SP, suggesting its neoplastic nature. Despite being uncommon, SP poses diagnostic challenges due to its resemblance to other lesions like squamous papilloma. The emergence of sialadenoma papilliferum-like intraductal papillary tumor (SP-IPT) further complicates its classification, emphasizing the need for thorough investigation. CASE PRESENTATION: A 50-year-old male presented with a left palatal lesion histologically diagnosed as SP-IPT. Surgical resection revealed characteristic features, including papillary projections into cystically dilated ductal spaces. Immunohistochemistry confirmed positivity for pan-keratin AE1/AE3, cytokeratin 7, SOX10, and BRAF V600E. Whole-exome sequencing identified BRAF V600E and PIK3CA H1047R mutations. No recurrence was observed three months post-excision. DISCUSSION: SP-IPT's diagnostic complexity stems from its resemblance to SP without an exophytic papillary component. However, shared BRAF mutations suggest a close relationship between the two entities. Similarities with skin adnexal tumors underscore the importance of molecular markers in tumor classification. The identification of PIK3CA mutation in SP-IPT adds to its molecular diversity, warranting further investigation into its clinical significance. CONCLUSION: This study presents a case of SP-IPT with unique histological and molecular features, highlighting its diagnostic and therapeutic challenges. The co-occurrence of BRAF V600E and PIK3CA H1047R mutations suggests a distinct molecular profile in SP-IPT, necessitating further research to elucidate its biological behavior and clinical implications.

Wholistic approach: Transcriptomic analysis and beyond using archival material for molecular diagnosis.

Many neoplasms remain unclassified after histopathological examination, which requires further molecular analysis. To this regard, mesenchymal neoplasms are particularly challenging due to the combination of their rarity and the large number of subtypes, and many entities still lack robust diagnostic hallmarks. RNA transcriptomic profiles have proven to be a reliable basis for the classification of previously unclassified tumors and notably for mesenchymal neoplasms. Using exome-based RNA capture sequencing on more than 5000 samples of archival material (formalin-fixed, paraffin-embedded), the combination of expression profiles analyzes (including several clustering methods), fusion genes, and small nucleotide variations has been developed at the Centre Léon Bérard (CLB) in Lyon for the molecular diagnosis of challenging neoplasms and the discovery of new entities. The molecular basis of the technique, the protocol, and the bioinformatics algorithms used are described herein, as well as its advantages and limitations.

Prevalence and distribution of cervical lymph node metastases in HPV-positive and HPV-negative oropharyngeal squamous cell carcinoma.

OBJECTIVE: In oropharyngeal squamous cell carcinoma (OP-SCC), the prevalence and distribution of clinical and pathological lymph node metastasis in the neck have been extensively reported. It served as the basis for consensus recommendations on the selection of the lymph node levels in the neck requiring a treatment. The objective of the study is to compare the prevalence and distribution of neck node metastases in HPV+ and HPV- OP-SCC from a large series of patients with OP-SCC who underwent a cervical lymph-node dissection (LND) as part of their treatment. METHODS: The study concentrated on OP-SCC patients treated by various neck node dissection (LND) procedures from January 2014 to December 2018 in 3 French institutions. Patients with prior head and neck cancer, prior neck surgery, the use of induction chemotherapy, or patients with carcinoma of unknown primary were excluded. HPV-status was assessed by p16 immunohistochemistry. For each patient, the clinical and the pathological nodal status, as well as the distribution of the positive nodes in each neck level (from Ia to V) were reported. RESULTS: Two-hundred and sixty-three patients were included (126 p16-negative (p16-), and 137 p16-positive (p16+). The rate of clinical positive node (cN+) reached 54% and 88.3% in the p16- and p16+ groups, respectively (p < 0.001); the corresponding rate of pathological positive node (pN+) reached 61.9% and 91.2%, respectively (p < 0.001). Regarding the clinical lymph node distribution, in p16+ patients, more positive nodes were observed in the ipsilateral level IV (p = 0.003), and less positive nodes were observed in the contralateral levels III and IV (p = 0.003 and p = 0.045, respectively). Regarding the pathologic lymph node distribution in the ipsilateral neck, in the cN0 patients, no significant difference was observed between p16- and p16+ patients (p = 0.33 to 1); in the cN+ patients, the nodes were distributed in levels Ib, II, III, IV and V without differences between the p16- and the p16+ patients. In the contralateral neck of p16- patients, nodes metastases were mainly observed in levels II, III and IV, whereas for the p16+ patients, positive nodes were only observed in level II (p = 0.03). CONCLUSION: This study demonstrated the higher prevalence of cN+ and pN+ in p16+ OP-SCC patients, but without meaningful difference in the distribution of the lymph node drainage between p16- and p16+ OP-SCC. It indicates that no difference should be made between p16- and p16+ patients regarding the extend of neck treatment.

Prediction of Oncotype DX recurrence score using deep multi-layer perceptrons in estrogen receptor-positive, HER2-negative breast cancer.

Oncotype DX (ODX) is a multi-gene expression signature designed for estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients to predict the recurrence score (RS) and chemotherapy (CT) benefit. The aim of our study is to develop a prediction tool for the three RS's categories based on deep multi-layer perceptrons (DMLP) and using only the morphoimmunohistological variables. We performed a retrospective cohort of 320 patients who underwent ODX testing from three French hospitals. Clinico-pathological characteristics were recorded. We built a supervised machine learning classification model using Matlab software with 152 cases for the training and 168 cases for the testing. Three classifiers were used to learn the three risk categories of the ODX, namely the low, intermediate, and high risk. Experimental results provide the area under the curve (AUC), respectively, for the three risk categories: 0.63 [95% confidence interval: (0.5446, 0.7154), p < 0.001], 0.59 [95% confidence interval: (0.5031, 0.6769), p < 0.001], 0.75 [95% confidence interval: (0.6184, 0.8816), p < 0.001]. Concordance rate between actual RS and predicted RS ranged from 53 to 56% for each class between DMLP and ODX. The concordance rate of low and intermediate combined risk group was 85%.We developed a predictive machine learning model that could help to define patient's RS. Moreover, we integrated histopathological data and DMLP results to select tumor for ODX testing. Thus, this process allows more relevant use of histopathological data, and optimizes and enhances this information.

Malignant melanoma with areas of rhabdomyosarcomatous differentiation arising in a giant congenital nevus with RAF1 gene fusion.

A girl, born with a posterior  lumbosacral giant congenital nevus, developed a central nodule that expanded over a period of 14 months into a 10-cm pedunculated mass. Histological analysis of the mass revealed melanoma of myxoid, small round-cell type with areas of  rhabdomyosarcomatous  transformation confirmed by immunohistochemistry. RNA sequencing identified an in-frame SASS6(e14)-RAF1(e8) fusion in both components and the nevus. A RAF1 FISH break-apart test found a balanced rearrangement pattern in the nevus and an unbalanced pattern in the malignant areas. Wild-type status of NRAS and BRAF was confirmed by NGS techniques. The array-CGH profile displayed copy number alterations commonly found in rhabdomyosarcomas. Despite intensive treatment, widespread metastatic evolution of the melanomatous component was observed.