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NTRK gene fusions have been described in a wide variety of central nervous system (CNS) and soft tissue tumors, including the provisional tumor type "spindle cell neoplasm, NTRK-rearranged" (SCN-NTRK), added to the 2020 World Health Organization Classification of Soft Tissue Tumors. Because of histopathological and molecular overlaps with other soft tissue entities, controversy remains concerning the lineage and terminology of SCN-NTRK.This study included 16 mesenchymal tumors displaying kinase gene fusions (NTRK fusions and one MET fusion) initially diagnosed as infantile fibrosarcomas (IFS), SCN-NTRK, and adult-type fibrosarcomas from the soft tissue, viscera and CNS. We used immunohistochemistry, DNA methylation profiling, whole RNA-sequencing and ultrastructural analysis to characterize them. Unsupervised t-distributed stochastic neighbor embedding analysis showed that 11 cases (2 CNS tumors and 9 extra-CNS) formed a unique and new methylation cluster, while all tumors but one, initially diagnosed as IFS, clustered in a distinct methylation class. All the tumors except one formed a single cluster within the hierarchical clustering of whole RNA-sequencing data. Tumors from the novel methylation class co-expressed CD34 and S100, had variable histopathological grades and frequently displayed a CDKN2A deletion. Ultrastructural analyses evidenced a myofibroblastic differentiation.Our findings confirm that SCN-NTRK share similar features in adults and children and in all locations combine an infiltrative pattern, distinct epigenetic and transcriptomic profiles, and ultrastructural evidence of a myofibroblastic lineage. Further studies may support the use of new terminology to better describe their myofibroblastic nature.

PD-L1 is an important predictive biomarker for treatment by immune checkpoint inhibitors (ICIs). ICIs are now indicated for the treatment of various cancer depending on the level of expression of PD-L1 on tumor cells. PD-L1 testing is done using immunohistochemistry with five different assays approved as companion diagnostic for ICIs. However, these assays have different score reporting methods and do not accurately measure PD-L1 expression. Exosomal PD-L1 testing has recently emerged as an alternative for cell-surface PD-L1 testing however studies are still premature and more extensive knowledge about this new potential biomarker is needed.Lay abstract Immunotherapy is a new strategy for cancer treatment that aims to reactivate the body’s own immune system, originally disabled by the tumor, to fight the malignancy. Immune checkpoint inhibitors are compounds developed for this purpose. However, their efficacy is subject to the abundance of their target, PD-L1, on the surface of cancer cells. Conventional PD-L1 testing through tumor biopsy has multiple technical drawbacks. Another form of PD-L1 secreted by the tumor into the circulation has emerged as a potential target for assessing immune checkpoint inhibitors efficacy but studies are still in their preliminary stages and further testing is required.

Resume Les acrometastases sont rares et peuvent etre exceptionnellement revelatrices d’un carcinome occulte. Le pronostic est souvent defavorable. L’imagerie ainsi que l’etude immunohistochimique sont indispensables pour determiner l’origine primitive et guider le traitement. Toutefois, dans certains cas les resultats de l’etude immunohistochimique peuvent etre trompeurs ; la correlation anatomoclinique devient fondamentale pour identifier l’origine de ces acrometastases. Nous rapportons un cas d’acrometastase au niveau du quatrieme doigt de la main gauche revelant un adenocarcinome pulmonaire chez un patient de 56 ans. L’etude histologique de la masse du doigt a revele un adenocarcinome mucosecretant d’architecture cribriforme. Les resultats de l’etude immunohistochimique etaient inhabituels. Les cellules tumorales presentaient une positivite diffuse cytoplasmique et granulaire avec les immunomarquages TTF1 et Hepar-1, sans marquage nucleaire avec le TTF1. Une tomodensitometrie thoraco-abdomino-pelvienne a confirme au niveau du lobe pulmonaire superieur gauche une masse tissulaire lobulee de 6 cm, qui a progresse malgre plusieurs seances d’immunochimiotherapie.

A 21-year-old man presented with left-sided facial paralysis and sensorineural hearing loss; physical examination was otherwise normal. What is your diagnosis?

Background Basal cell carcinoma (BCC) represents by far the most common non-melanoma skin cancer (NMSC) in the world with an increasing incidence of 3% to 10% per year, especially in patients under the age of 40. While variants in the sonic Hedgehog and cell cycle regulation pathways account for the majority of BCC cases in adults, the molecular etiology of BCC in young patients is unelucidated yet. This study aims to investigate the molecular profile of BCC in the young population. Methods 28 tumors belonging to 25 Lebanese patients under the age of 40, presenting different stages of BCC and diagnosed at Hôtel Dieu de France—Saint Joseph University Medical Center were included in this study. A selected panel of 150 genes involved in cancer was analyzed by Next Generation Sequencing (NGS) in the 28 included tumors. Results Genetic variants detected in more than 5% of the reads, with a sequencing depth ≥ 50x, were selected. Two hundred and two genetic variants in 48 different genes were detected, with an overall average sequencing depth of 1069x. Among the 28 studied tumors, 18 (64.3%) show variations in the PTCH1 gene, 6 (21.4%) in TP53 and 3 (10.7%) in SMO. Conclusions This is the first study reporting NGS-based analysis of BCC in a cohort of young patients. Our results highlight the involvement of the hedgehog and cell cycle regulation pathways in the genesis of BCC in the general population. The inclusion of a larger cohort of young patients is needed to confirm our findings.

Acrometastasis are rare and can be exceptionally indicative of an occult carcinoma. The prognosis is generally poor. The radiological and immunohistochemical findings can be of great value to determine the primary and to guide treatment. We report a case of a 56-years-old man with acrometastasis at the fourth finger of the left hand revealing a pulmonary adenocarcinoma. Histopathological analysis showed a cribriform adenocarcinoma with an unusual cytoplasmic co-expression of TTF1 and Hepar-1 upon immunohistochemical analysis. There was no nuclear TTF1 immunostaining. Imaging explorations showed a 6-cm mass of the left superior pulmonary lobe. The patient received immunochemotherapy. Upon follow-up, there was evidence of disease progression on chest computed tomography scan.

Aim: Report the epidemiologic and histologic characteristics of CNS lesions in the Lebanese population. Methods: We conducted a retrospective study evaluating 2025 CNS lesions diagnosed between 1998 and 2017 in the pathology laboratory of a Lebanese tertiary center. Results: 52.2% of patients were men with a median age of 50 years. The most frequent symptoms were epilepsy (22.5%), headache (20.6%) and motor impairment (19.9%). 90.7% of tumors were primary. Lung (35.6%) and breast (16.5%) were the most frequent primaries of metastases. 46.2% of primary CNS tumors were glial, predominantly astrocytic (56.4%), and (42.5%) were nonglial, predominantly meningeal tumors (58%). Conclusion: Compared with Western literature, the Lebanese population is characterized by a younger age of onset of brain tumors, a lower rate of meningiomas and a higher rate of gliomas.

Resume Cette observation concerne une femme de 25 ans sans antecedents qui consulte, en post-partum (accouchement sans complications), pour expulsion spontanee par voie vaginale d’un nodule bien limite de 4 cm correspondant a une tumeur myofibroblastique inflammatoire. L’analyse morphologique et immunohistochimique couplee a une analyse par FISH a permis de poser le diagnostic.

We report the case of a 34-year-old woman presenting a 10cm axillary mass diagnosed as hybrid tumor low-grade fibromyxoid sarcoma/sclerosing epithelioid fibrosarcoma. Microbiopsy for morphological and immunohistochemical analyses was associated with molecular analysis (FISH and PCR) to confirm the diagnosis.

e13544 Background: Lesions of the central nervous system (CNS) are a heterogeneous group of tumoral and non-tumoral lesions, benign or malignant, primary or metastatic. The overall incidence rate of all brain tumors is estimated to be 10.82 per 100 000 person-years. There is no data in Lebanon characterizing the CNS lesions. The aim of our study is to report the epidemiologic and histologic characteristics of these lesions in a Lebanese tertiary center. Methods: This is a retrospective study evaluating the characteristics of the CNS lesions diagnosed in 20 years (from January 1998 to June 2017) in the pathology laboratory of Hôtel Dieu de France, Saint Joseph University hospital of Beirut, Lebanon. The data were extracted from the computerized records of the laboratory. Different variables were evaluated, from the samples types and epidemiologic characteristics, to the revealing symptoms and the histologic subtypes. Statistical analysis was performed using SPSS 24.0. Results: 2025 tumoral lesions over 20 years were interpreted. 25.4% of the samples were obtained by biopsy, 65% by surgical resection, 3.7% were cerebral spinal fluid and 5.9% were undetermined. 52.2% of the patients were men and 47.8% were women with a median age of 50 years, from 0 to 89 years. The most frequent revealing symptoms were epilepsy (22.5%), headache (20.6%) and motor impairment (19.9%). 90.7% of the CNS tumors were primary and 9.3% were metastatic. Lung (35.6%) and breast (16.5 %) were the two most frequent primaries of the metastatic lesions. 46.2% of primary CNS tumors were glial, 42.5% non-glial, 3.5% mixed neuroglial and 6.4% mesenchymal. The two most frequent glial tumors were astrocytic (56.4%) and oligodendroglial (17.9%) tumors, while the most frequent non-glial tumors were meningeal tumors (58%) and cranial nerve and paraspinal tumors (16.3%). Conclusions: The histological and epidemiological characteristics of brain tumors in Lebanon are consistent in many features with what is known in the literature, but the Lebanese population differs by a younger age of onset, a lower rate of meningiomas, and a higher rate of gliomas.

Neuroendocrine tumors represent 20% of primary lung neoplasms in some registries. According to the WHO classification of 2004, reconsidered for 2015, these lung tumors are divided into 4 groups: typical and atypical carcinoid, small cell and large cell neuroendocrine carcinomas. We report in this paper, for the first time in Lebanon, the distribution and the population characteristics of these tumors.This descriptive retrospective study concerned all the pulmonary neuroendocrine tumors (NET) with their characteristics diagnosed in Hotel Dieu de France in Beirut, Lebanon from 2001 to 2012, with attention to features like age, gender and subgroup.Of 194 patients with pulmonary NET, 12.4% were typical carcinoid tumors, 3.6% atypical carcinoid, 66.5% small cell lung cancer, 7.7% combined small cell carcinomas and 9.8% large cell neuroendocrine tumors. The mean ages of patients were respectively 51.2 years in typical carcinoid, 64 years in atypical carcinoid, 64.2 years in small cell lung cancers, 67.2 in combined small cell lung cancer and 66.9 in large cells neuroendocrine tumors. The M/F sex ratios were respectively 0.3, 1.3, 1.4, 2.7 and 2.2.The characteristics of lung neuroendocrine tumors in our Lebanese institution are comparable to those reported in the literature.

We report the case of a 34-year-old woman presenting a 10cm axillary mass diagnosed as hybrid tumor low-grade fibromyxoid sarcoma/sclerosing epithelioid fibrosarcoma. Microbiopsy for morphological and immunohistochemical analyses was associated with molecular analysis (FISH and PCR) to confirm the diagnosis.