P. Amico’s research while affiliated with Policlinico di Bari and other places

Key Clinical Message Ependymomas are primary brain tumors that predominantly affect individuals between 0 and 4 years of age. Although ependymomas have a propensity for recurrence and the potential to spread within the central nervous system through cerebrospinal fluid (resulting in drop metastases), reports of extra‐neural metastatic localizations are exceedingly rare in the existing literature. This case report presents a unique and rare instance of recurrent intracranial anaplastic ependymoma with a late‐onset giant scalp metastasis. Abstract A 55‐year‐old male patient with a medical history of partial resection of an atypical supratentorial left temporal ependymoma presented with a recurrent anaplastic ependymoma, which had been managed with surgery and radiotherapy. After a 4‐year follow‐up, the patient developed a subcutaneous mass in the left parietal region of the scalp. A multidisciplinary team of neurosurgeons and plastic surgeons performed a surgical procedure, which included en bloc removal of the scalp lesion, resection of 1 cm of unaffected skin, and craniotomy to address an osteolytic area in the parietal skull bone. Skin autografts were used for reconstruction. Histological examination confirmed metastasis of anaplastic ependymoma in the scalp. After a delay in starting chemotherapy due to concerns related to the COVID‐19 pandemic, the patient eventually initiated chemotherapy, leading to disease stability at a short‐term follow‐up. Scalp metastases from ependymoma are rarely reported in the literature. Management of such cases necessitates aggressive surgical resection, followed by adjuvant chemotherapy and radiotherapy. A multidisciplinary approach is recommended to ensure effective and targeted therapy, with a focus on preserving aesthetics, particularly in pediatric cases.

Pembrolizumab has received approval as a first-line treatment for unresectable/metastatic triple-negative breast cancer (mTNBC) with a PD-L1 combined positive score (CPS) of ≥ 10. However, assessing CPS in mTNBC poses challenges. Firstly, it represents a novel analysis for breast pathologists. Secondly, the heterogeneity of PD-L1 expression in mTNBC further complicates the assessment. Lastly, the lack of standardized assays and staining platforms adds to the complexity. In KEYNOTE trials, PD-L1 expression was evaluated using the IHC 22C3 pharmDx kit as a companion diagnostic test. However, both the 22C3 pharmDx and VENTANA PD-L1 (SP263) assays are validated for CPS assessment. Consequently, assay-platform choice, staining conditions, and scoring methods can significantly impact the testing outcomes. This consensus paper aims to discuss the intricacies of PD-L1 CPS testing in mTNBC and provide practical recommendations for pathologists. Additionally, we present findings from a nationwide Italian survey elucidating the state-of-the-art in PD-L1 CPS testing in mTNBC.

Introduction Malignant peripheral nerve sheath tumors (MPNSTs) are a group of rare soft tissue sarcomas of mesenchymal origin. These tumors generally require extensive local excision owing to their aggressive potential. Though the role of radiotherapy is controversial, in this report, we present the case of an MPNST in the forearm that was treated with microsurgery followed by image-guided radiation therapy to achieve complete tumor disappearance at the 18-month follow-up. Case report A 69-year-old woman with underlying paranoid schizophrenia was referred to our department with pain, severe swelling, and ecchymosis of her right forearm. Physical examination showed hypoesthesia in the segments innervated by the median nerve and reduced motor strength of her right hand. A gadolinium-enhanced MRI showed a large malignant peripheral nerve sheath tumor (13 x 8 x 7 cm) of the median nerve in the forearm. She underwent microsurgical en-bloc tumor resection with sparing of the median nerve. Thirty-five days postoperatively, she underwent image-guided radiotherapy (IGRT) using volumetric modulated arc therapy (VMAT). Serial MRI scans of the forearm with Gadolinium and whole-body CT scan with contrast enhancement at 30 days, 6 months, 1 year, and 18 months postoperatively documented no tumor recurrence, remnants, or metastases. Conclusions In this report, we demonstrate the successful use of advanced radiotherapy techniques such as IGRT while avoiding demolitive surgery for MPNST. Though a longer follow-up is necessary, at the 18-month follow-up, the patient demonstrated good outcomes from surgical resection followed by adjuvant RT for MPNST in the forearm.

Background As the European population with Spinal Cord Injury (SCI) is expected to become older, a better understanding of ageing with SCI using functioning, the health indicator used to model healthy ageing trajectories, is needed. We aimed to describe patterns of functioning in SCI by chronological age, age at injury and time since injury across eleven European countries using a common functioning metric, and to identify country-specific environmental determinants of functioning. Methods Data from 6’635 participants of the International Spinal Cord Injury Community Survey was used. The hierarchical version of Generalized Partial Credit Model, casted in a Bayesian framework, was used to create a common functioning metric and overall scores. For each country, linear regression was used to investigate associations between functioning, chronological age, age at SCI or time since injury for persons with para- and tetraplegia. Multiple linear regression and the proportional marginal variance decomposition technique were used to identify environmental determinants. Results In countries with representative samples older chronological age was consistently associated with a decline in functioning for paraplegia but not for tetraplegia. Age at injury and functioning level were associated, but patterns differed across countries. An association between time since injury and functioning was not observed in most countries, neither for paraplegia nor for tetraplegia. Problems with the accessibility of homes of friends and relatives, access to public places and long-distance transportation were consistently key determinants of functioning. Conclusions Functioning is a key health indicator and the fundament of ageing research. Enhancing methods traditionally used to develop metrics with Bayesian approach, we were able to create a common metric of functioning with cardinal properties and to estimate overall scores comparable across countries. Focusing on functioning, our study complements epidemiological evidence on SCI-specific mortality and morbidity in Europe and identify initial targets for evidence-informed policy-making.

Background/aim: Extraventricular supratentorial ependymomas are rare entities. Most ependymomas are located at the infratentorial and intraventricular level, and only in a small group of cases they do not present continuity with the ventricular system. This is a case report of a patient with an atypical location of a cerebral ependymoma, which required the implementation of a complex and infrequent approach for its complete microsurgical removal. Case report: A 16-year-old male patient was referred at our department with a diagnosis of a 40 mm × 50 mm × 60 mm solid-cystic space-occupying lesion, sited between the left superior frontal-cingulate gyri. A contralateral transfalcine interhemispheric approach was selected, which achieved total resection of the tumor. The histopathological diagnosis of Grade II ependymoma was obtained according to WHO classification. Conclusion: The contralateral transfalcine interhemispheric approach represents a favorable surgical corridor to achieve a total resection of the tumor lesion and is favored by an adequate working angle and reduced brain manipulation.

Background Primary intracranial ependymomas (IE) are rare brain tumors rarely metastasizing outside the central nervous system. We systematically reviewed the literature on extra-neural metastases from primary IEs. Methods PubMed, Scopus, Web-of-Science, and Cochrane were searched following the PRISMA guidelines to include studies of extra-neural metastases from primary IEs. Clinical features, management strategies, and survival were analyzed. Results We collected 48 patients from 43 studies. Median age was 13 years (range, 2-65). Primary IEs were frequently located in the parietal (22.9%) and frontal (16.7%) lobes, and mostly treated with resection (95.8%) and/or radiotherapy (62.5%). Most IEs were of grade-III (79.1%), and few of grade-I (6.3%) or grade-II (14.6%). 45 patients experienced intracranial recurrences, mostly treated with resection (86.7%), radiotherapy (60%), and/or chemotherapy (24.4%). Median time-interval from primary IEs was 28 months (range, 0-140). Most extra-neural metastases were diagnosed at imaging (37.5%) or autopsy (35.4%). Extra-neural metastases were multifocal in 38 patients (79.1%), mostly involving cervical or hilar lymph-nodes (66.7%), lung/pleura (47.9%), and/or scalp (29.1%). Surgical resection (31.3%), chemotherapy (31.3%) and locoregional radiotherapy (18.8%) were the most common treatments for extra-neural metastases, but 28 (58.3%) patients were not treated. At last follow-up, 37 patients died with median overall-survivals from primary IEs of 36 months (range, 1-239), and from extra-neural metastases of 3 months (range, 0.1-36). Overall-survival was significantly longer in patients with grade-I and II IEs (P=0.040). Conclusion Extra-neural metastases from primary IEs are rare, but mostly occur at later disease stages. Multidisciplinary management strategies should be intended mostly for palliation.

Background Acrometastases, secondary tumors affecting oncological patients with systemic metastases, are associated with a poor prognosis. In rare cases, acrometastases may precede establishing the primary tumor diagnosis. Case Description A 72-year-old female heavy smoker presented with low back pain, and right lower extremity sciatica/radiculopathy. X-rays, CT, MR, and PET-CT scans documented primary lung cancer with multi-organ metastases and accompanying pathological fractures involving the sacrum (S1) and right 4 th digit. She underwent a S1 laminectomy and amputation of the distal phalanx of the right fourth finger. The histological examination documented a poorly differentiated pulmonary adenocarcinoma infiltrating bone and soft tissues in the respective locations. The patient was treated with a course of systemic immunotherapy (i.e. pembrolizumab). At 6-month follow-up, the patient is doing well and can stand and walk without pain. Conclusion Spontaneous sacral fractures may be readily misdiagnosed as osteoporotic and/or traumatic lesions. However, in this case, the additional simultaneous presence of a lytic finger lesion raised the suspicion that these were both metastatic tumors. Such acrometastases, as in this case attributed to a lung primary, may indeed involve the spine.

Background and Objectives: The term acrometastases (AM) refers to secondary lesions sited distally to the elbow and knee, representing 0.1% of all bony metastases. By frequency, pulmonary cancer and gastrointestinal and genitourinary tract neoplasms are the most responsible for the reported AM. Improvements in oncologic patient care favor an increase in the incidence of such rare cases. We performed a systematic review of acrometastases to the hand to provide further insight into the management of these fragile patients. We also present a peculiar case of simultaneous ac-rometastasis to the ring finger and pathological vertebral fracture. Material and Methods: A literature search according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement was conducted using the PubMed, Google Scholar, and Scopus databases in De-cember 2020 on metastasis to the hand and wrist, from 1986 to 2020. MeSH terms included acrome-tastasis, carpal metastasis, hand metastasis, finger metastasis, phalangeal metastasis, and wrist me-tastasis. Results: In total, 215 studies reporting the follow-up of 247 patients were analyzed, with a median age of 62 years (range 10-91 years). Overall, 162 out of 247 patients were males (65.6%) and 85 were females (34.4%). The median reported follow-up was 5 months (range 0.5-39). The median time from primary tumor diagnosis to acrometastasis was 24 months (range 0.7-156). Acrometasta-ses were located at the finger/phalanx (68.4%), carpal (14.2%), metacarpal (14.2%), or other sites Citation: Umana, G.E.; Scalia, G.; Passanisi, M.; Palmisciano, P.; Da Ros, V.; Pompili, G.; Barone, F.; Amico, P.; Tomasi, S.O.; Graziano, F.; et al. Acrometastases to the Hand: A Systematic Review. Medicina 2021, 57, 950. https://doi.

Due to the high expression of P-selectin glycoprotein ligand-1 (PSGL-1) in lymphoproliferative disorders and in multiple myeloma, it has been considered as a potential target for humoral immunotherapy, as well as an immune checkpoint inhibitor in T-cells. By investigating the expression of SELPLG in 678 T- and B-cell samples by gene expression profiling (GEP), further supported by tissue microarray and immunohistochemical analysis, we identified anaplastic large T-cell lymphoma (ALCL) as constitutively expressing SELPLG at high levels. Moreover, GEP analysis in CD30+ ALCLs highlighted a positive correlation of SELPLG with TNFRSF8 (CD30-coding gene) and T-cell receptor (TCR)-signaling genes (LCK, LAT, SYK and JUN), suggesting that the common dysregulation of TCR expression in ALCLs may be bypassed by the involvement of PSGL-1 in T-cell activation and survival. Finally, we evaluated the effects elicited by in vitro treatment with two anti-PSGL-1 antibodies (KPL-1 and TB5) on the activation of the complement system and induction of apoptosis in human ALCL cell lines. In conclusion, our data demonstrated that PSGL-1 is specifically enriched in ALCLs, altering cell motility and viability due to its involvement in CD30 and TCR signaling, and it might be considered as a promising candidate for novel immunotherapeutic approaches in ALCLs.

Background Ovarian brain metastases represent a very rare occurrence and without treatment, prognosis is very poor, with a median survival of one month. We present a unique case of a patient affected by a giant cystic intracerebral metastasis (>7 cm) secondary to an ovarian papillary serous adenocarcinoma, along with a review of the literature regarding large cystic ovarian metastases and their management. Case description A 49-years-old female patient was admitted to our institution because she presented progressive headache and altered consciousness. Brain computed tomography (CT) scan and magnetic resonance imaging (MRI) revealed the presence of a giant left frontal intracerebral cystic lesion. The patient underwent a surgical removal of an ovarian high-grade papillary serous adenocarcinoma three years before. We performed a left frontal craniotomy and microsurgical removal of the brain lesion, achieving a safe macroscopic total resection, thanks to intraoperative neurophysiological monitoring (IONM). The post-operative period was uneventful with a complete recovery. Post-operative brain MRI showed a complete removal of the lesion. Conclusions The presence of a giant cystic metastasis with symptoms of intracranial hypertension needs a radical and safe surgical removal, along with the management of a multidisciplinary oncologic group.