Primary intraosseous papillary intralymphatic angioendothelioma of the distal femoral epiphysis: a case report with literature review.

INTRODUCTION: Papillary intralymphatic angioendothelioma (PILA) is an exceptionally rare metastasizing soft tissue tumor. It tends to arise in the subcutaneous tissues of distal extremities in children. Only four intraosseous PILA cases have been reported until now in English language literature. CASE REPORT: We present a case of PILA arising in the distal femoral epiphysis of a 50-year-old female patient. It started as a relentless pain in her left knee. A plain radiography revealed a radiolucent area in the left internal femoral condyle. Computerized tomography revealed a 1-cm lytic lesion with a sclerotic rim. Magnetic resonance images showed a significant bone marrow edema signal focused on a 1-cm subchondral lesion suggestive of an intraarticular osteoid osteoma. Histologically, the tumor contained vascular channels covered by a single endothelial layer with intraluminal papillary endothelial structures lined with hobnail cells. Immunohistochemically, the cells were positive for ERG, CD31, and D2-40. The tumor underwent cryoablation and 6 months later, after local recurrence or tumor persistence, a wide tumor resection was referred. After 7 years of follow-up, the patient displayed neither local recurrence nor distant metastases. CONCLUSION: Primary intraosseous PILAs are exceedingly rare tumors that should be considered in the differential diagnosis of vascular bone tumors.

Comparison of maternal, fetal, obstetric and neonatal outcomes for 234 triplet pregnancies conceived in vivo versus IVF and ICSI conceptions.

RESEARCH QUESTION: Is there a difference in maternal, fetal, obstetric and neonatal outcomes for triplet pregnancies when comparing in vivo conceptions with those conceived by assisted reproductive technology (ART)? DESIGN: This single-centre, retrospective cohort study included all triplet pregnancies followed up at La Paz University Hospital, Madrid between 2000 and 2022. The characteristics of the pregnant women, and maternal, fetal, obstetric and perinatal outcomes were examined. Univariate and multivariate statistical analyses were performed. RESULTS: In total, 234 triplet pregnancies were analysed: 92 in the natural and assisted insemination conception group (in-vivo conception) and 142 in the in vitro fertilization and intracytoplasmic sperm injection conception group (ART conception). ART triplet pregnancies were more common between 2000 and 2010 (P = 0.003). The percentage of monochorionic triamniotic pregnancies was significantly higher (P = 0.02) in the in-vivo conception group, and the percentage of dichorionic triamniotic pregnancies was significantly higher (P = 0.003) in the ART conception group. After adjusting for confounders, intrauterine growth restriction (IUGR) remained significantly more common in the ART conception group (adjusted odds ratio 8.65, 95% CI 1.66-45.03; P = 0.01). Differences in maternal age (P = 0.61), threatened preterm labour (P = 0.10), Apgar score ≤5 at 5 min (P = 0.99), umbilical cord pH <7.20 (P = 0.99) and fetal death (P = 0.99) disappeared after adjustment for confounders. CONCLUSION: ART triplet pregnancies had a higher rate of IUGR than in vivo triplet pregnancies. This could be related to higher maternal age, and higher rates of Apgar score ≤5 at 5 min and umbilical cord pH <7.20 in these pregnancies. In these cases, placental examination could provide valuable information.

Primary aneurysmal bone cyst of hands and feet: A series of 14 cases.

Aneurysmal bone cyst (ABC) is a relatively rare, benign bone tumor that occurs exceptionally in the hands and feet. The objective of this article is to present clinical, radiological, histopathological features and management of a series of 14 primary ABC cases in these unusual locations. Eight cases occurred in hands and six in feet. We present the first reported subungual case to occur in the hand. The average age of the patients was 26 years (range 7 to 49), with half being over the age of twenty at diagnosis. The male to female ration was 9:5. In radiological terms, ABC appeared as an expansive lesion with internal septa and without cortical disruption. Twelve cases displayed the classic multicystic morphology and two cases were of the solid variant. "Blue bone" was detected in 50 % of the specimens. Treatment consisted of curettage, excision, or amputation in all cases. Recurrence rate was observed in 35 % of the cases, with the similar ABC morphology as the original samples. New therapeutic options have been proposed on their own or in combination with surgery to reduce local recurrence rates.

First Reported Case of Malignant Ectomesenchymoma with p.Leu122Arg Mutation in MYOD1 Gene: Extensive Intra- and Extracranial Tumor in a 15-Year-Old Female.

BACKGROUND: Ectomesenchymomas (EMs) are extremely rare neoplasms composed of malignant mesenchymal components and neuroectodermal derivatives. They are described in a wide variety of locations, with the head and neck region being one of the most frequently involved areas. EMs are usually managed as high-risk rhabdomyosarcomas and have similar outcomes. METHODS: We present the case of a 15-year-old female with an EM that arose in the parapharyngeal space and extended into the intracranial space. RESULTS: Histologically, the tumor presented an embryonal rhabdomyosarcomatous mesenchymal component and the neuroectodermal component was constituted by isolated ganglion cells. Next-generation sequencing (NGS) revealed a p.Leu122Arg (c.365 T > G) mutation in the MYOD1 gene, a p.Ala34Gly mutation in the CDKN2A gene, and CDK4 gene amplification. The patient was treated with chemotherapy. She died 17 months after the debut of symptoms. CONCLUSION(S): To our knowledge, this is the first reported case in English literature of an EM with this MYOD1 mutation. We suggest combining PI3K/ATK pathway inhibitors in these cases. NGS should be performed in EMs cases to detect mutations with potential treatment options.

Giant thigh glomus tumor of uncertain malignant potential: Case report with pathologic-radiologic correlation.

INTRODUCTION: Glomus tumors (GT) are rare, benign tumors that arise from glomus bodies and usually develop in digital areas. Extradigital GT are exceptional and thigh location is infrequent. CASE REPORT: We report a case of a GT of the thigh in a 79-year-old male patient that measured 9.5 cm in maximum size. The GT lay above the muscular fascia without infiltrating it. Internal hypervascularity was seen by spectral Doppler ultrasound. Magnetic resonance image showed a heterogeneous mass with hyperintense and hypointense components and internal lobes with liquid-liquid levels. Histopathology revealed a monotonous round-cell proliferation with central nuclei without atypia or mitotic figures, around small-caliber vessels. These cells expressed smooth muscle actin and pericellular collagen IV. GT of uncertain malignant potential was diagnosed. The mass was completely removed. The patient did not experience local relapse nor distant metastasis. CONCLUSION: GT are rare soft tissue tumors whose diagnosis of unusual giant masses in uncommon locations may be delayed and misdiagnosed given the low suspicion.

Primary intraosseous alveolar soft part sarcoma: Report of two cases with radiologic-pathologic correlation.

Alveolar soft part sarcoma (ASPS) accounts for less than 1 % of all soft tissue sarcomas. ASPS presents a poor prognosis and develops frequent metastases, especially in the lungs, brain and bones. Current therapies, such as surgery, radiotherapy and chemotherapy, are not fully effective and other alternative treatments are currently being studied. ASPS is predominantly found in the deep soft tissues of the lower extremities. To our knowledge, only thirteen primary intraosseous ASPS have been reported in the literature. In this study, we report two new cases of this exceedingly rare entity. Both cases already had multiple metastases since diagnosis; one of them represents the first case of a primary bone ASPS in the ulna and is also the primary intraosseous ASPS with the longest reported case of survival, after having maintained long periods of stabilization despite not having received any systemic treatment.

Fibrous hamartoma of infancy. Radiologic-pathologic study of 21 cases: 8 with predominant pseudoangiomatous pattern.

Fibrous hamartoma of infancy (FHI) is a very rare benign soft tissue lesion that principally affects the axilla, trunk, and upper extremities of children younger than 2 years. It is usually cured by local excision. Histologically, these lesions have a triphasic morphology in an organoid pattern: mature adipose tissue, fibroblastic/myofibroblastic trabeculae, and small round cell nests in a myxoid matrix. However, morphologic variants have recently been described. Focal areas with a pseudoangiomatous pattern have been found in some FHI, but few cases with predominant pseudoangiomatous areas have been previously described in the medical literature. We report 21 new cases of FHI, 8 of them with a predominant pseudoangiomatous pattern. Our cases with a predominant pseudoangiomatous pattern did not present specific radiological findings.

Calcifying aponeurotic fibroma: Radiologic-pathologic analysis of ten cases and review of the literature.

Calcifying aponeurotic fibroma (CAF) is a very rare benign entity that principally affects the volar fascia, tendons, and aponeuroses of the hands and feet with a peak incidence of between 5 and 15 years, although there have been cases found for a wide age range and at various anatomical sites. We present ten CAF cases; consisting of eight children and two adults. CAF occurred in the extremities in nine of the cases and in the chest wall in one case. CAF ultrasound and radiological findings are nonspecific but may help orientate diagnosis. Magnetic resonance imaging should be performed when there are doubtful cases, when occurring in nontypical sites, and when there are cases of nontypical clinical presentation. Histologically, all cases showed two components, a fibromatosis-like component and a nodular component. Chondroid areas were present in five cases. Calcifications were observed in nine cases. ERG immunostaining showed the same patterns in all the cases; diffuse positivity in pericalcified areas, and patchy positivity in areas away from calcifications. CAF has distinctive histopathological features which should aid in the differential diagnoses with other entities.

[Translated article] Oligometastases in oncological orthopaedic surgery. Our experience.

OBJECTIVE: To analyse the incidence and survival of patients with oligometastases (solitary and normal) when they are treated in centres that are experts in multidisciplinary approach to patients with sarcoma. MATERIAL AND METHOD: Retrospective analysis of 414 patients with bone metastases secondary to carcinomas at Hospital Universitario La Paz and Hospital MD Anderson Cancer Centre (Madrid) between May 2006 and May 2019. Metastases located in the pelvis and axial skeleton were excluded, analyzing a total of 28 patients who met the criterion for solitary metastases or oligometastases with normal criteria. The study survival estimate was carried out following the Kaplan-Meier statistical method. RESULTS: The survival of the patients following the oligometastases criteria (solitary and normal) was 53%. Breast cancer was the most prevalent and had a survival rate of more than 70%. The average age of the patients was 58 years old. DISCUSSION: Systemic treatments in cancer treatment have managed to improve disease-free survival curves and lead us to redirect on the paradigm for the treatment of oligometastases, stating that treatment should be carried out in the centres that are experts in the treatment of sarcomas. CONCLUSIONS: The choice of surgical treatment for patients with oligometastases in the strict sense (solitary) and normal should be evaluated by multidisciplinary teams according to the prognoses of the patient, anatomical location and histotype of the neoplasm.

Expression of clec9a in the oral cancer microenvironment. A preliminary immunohistochemical pilot study.

BACKGROUND: The search for treatments to improve cancer survival has led to the emergence of immunotherapy and the study of the tumour microenvironment existing in neoplasms. This preliminary study aims to understand the clinical and pathological relationship of clec9a expression in oral cancer and to explore survival models for future studies. MATERIAL AND METHODS: Immunohistochemical study that included 26 patients with a diagnosis of oral squamous cell carcinoma (OSCC) in mobile tongue and floor of the mouth. Clinical and histopathological variables were recorded, and the biomarkers clec9a for dendritic cells and CD8 and CD4 for lymphocytes were used. RESULTS: Clec9a was expressed in 58% of the sample. It was more common in cases with low lymphoplasmacytic infiltration and in type 2 invasion patterns. It was significantly related to CD8 expression (p=0.055 and p=0.007). No prognostic risks were evident in the survival models studied (overall survival, disease-specific survival, disease-free survival). CONCLUSIONS: CLEC9A expression is present in the OSCC microenvironment and is mainly related to the presence of CD8 lymphocytes. The relationship of its expression with survival prognosis in OSCC could not be confirmed; however, this needs to be confirmed through future studies with larger sample size.

Oral mucositis. Is it present in the immunotherapy of the immune checkpoint pd1/pd-l1 against oral cancer? A systematic review.

BACKGROUND: Oral mucositis (OM) is a painful lesion that takes place in the mucosa of the oral cavity, usually its etiology is associated with drug therapies in cancer patients. It is presented as well-defined ulcers whose painful symptomatology sometimes implies the suspension of oncological treatment or parenteral feeding, being therefore an important adverse effect, marking the evolution of these types of therapies against cancer. The present work aim is to know the prevalence of oral mucositis in oral cancer immunotherapy compared to its prevalence in standard therapy. MATERIAL AND METHODS: A protocol was developed for a systematic review following PRISMA® guidelines and a focused question (PICO) was constructed. A comprehensive literature search was conducted on electronic databases including PubMed, the SCOPUS database, the Cochrane library and the Web of Science (WOS). RESULTS: Six clinical trials were included that met the different inclusion criteria. In these articles, a discrepancy between the prevalence of OM in patients treated with chemotherapy and patients treated with immunotherapy related to the immune checkpoint PD-1/PD-L1 (Nivolumab and Pembrolizumab) was observed. CONCLUSIONS: The prevalence of oral mucositis is lower in new immunotherapy with monoclonal antibodies against oral cancer than drugs used so far (chemotherapy drugs [methotrexate, cisplatin] as well as cetuximab). However, more studies should be carried out to confirm these data.

Genetic predisposition to fetal and neonatal cancer.

BACKGROUND: Neonatal tumors represent an extremely rare and heterogeneous disease with an unknown etiology. Due to its early onset, it has been proposed that genetic factors could play a critical role; however, germline genetic analysis is not usually performed in neonatal cancer patients PATIENTS AND METHODS: To improve the identification of cancer genetic predisposition syndromes, we retrospectively review clinical characteristics in 45 patients with confirmed tumor diagnosis before 28 days of age, and we carried out germline genetic analysis in 20 patients using next-generation sequencing and directed sequencing. RESULTS: The genetic studies did not find any germline mutation except patients diagnosed with bilateral retinoblastoma who harbored RB1 germline mutations. CONCLUSIONS: Our results suggest that genetic factors have almost no higher impact in most neonatal tumors. However, since the heterogeneity of the tumors and the small sample size analyzed, we recommend complementary and centralized germline studies to discard the early onset as an additional criterion to take into account to improve the identification of cancer genetic predisposition syndromes in neonates.

Prognostic value of neutrophil-to-lymphocyte ratio and other inflammatory markers in patients with high-risk soft tissue sarcomas.

BACKGROUND: Soft tissue sarcomas (STS) have a high risk of relapse in spite of the use of (neo)adjuvant chemotherapy. In this context, looking for new prognostic biomarkers is an interesting field of research. Our aim is to analyze the prognostic impact of neutrophil-to-lymphocyte ratio (NLR) and other serum markers in patients with STS who received chemotherapy with curative intent. MATERIALS AND METHODS: This is a retrospective observational study. We included all patients with STS (primary tumor, local recurrence or resected metastatic disease) treated with high-dose ifosfamide and epirubicin with curative intent from January 2007 to December 2018. The pretreatment NLR and other serum markers were calculated, selecting the median as the cut-off value for the survival and multivariate analysis. RESULTS: Seventy-nine patients were included. Median NLR, platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR) were 2.83, 174.05 and 3.25, respectively. Median progression-free survival (PFS) was significantly longer in patients with low NLR [not reached (NR) vs 21, 92 months, P < 0.01]. No significant differences were found for PFS regarding PLR or LMR. For overall survival (OS), a significant survival advantage was also found for patients with low NLR (NR vs 65.45 months, P = 0.01), without differences for PLR or LMR. In multivariate analysis, NLR remains an independent prognostic factor for PFS. CONCLUSION: In our cohort, low NLR was significantly associated with a longer PFS and OS, and is consolidated as an independent prognostic factor.

Oral squamous cell carcinoma of tongue: Histological risk assessment. A pilot study.

BACKGROUND: More than 90% of malignant tumors diagnosed in the oral cavity are Oral Squamous Cell Carcinomas (OSCC) whose preferred location is the tongue. Classically, this disease has affected men preferentially, although recent studies suggest that trends are changing and the proportion of women with OSCC is increasing. In addition, the prevalence of oral cancer is also determined by some risk factors as alcohol consumption and tobacco. Currently, the Tumor, Node, Metastasis (TNM) classification is employed to defined tumor stage and based on this guide specific treatments are established. However, 5-year-survival does not exceed 50% of cases. The objective of this study is to determine whether a histological risk pattern indicative of higher recurrence might be present in T1-T2 tumors located in the anterior two thirds of the tongue. MATERIAL AND METHODS: Samples from 26 patients with OSCC were analyzed and histological risk pattern of recurrent and non-recurrent tumors were compared. We have analyzed histological variables described in Anneroth and Brandwein-Gensler classifications. Additionally, we have also examined both clinical variables such as age, sex or comorbidities, as well as habits such as tobacco or alcohol consumption. RESULTS: We found that sex (male) and keratinization degree (high or moderate) are directly related with OSCC recurrence. In fact, free illness time is lower in men and higher in those cases with minimal or no keratinization. CONCLUSIONS: Based on the variables analyzed, it has not been possible to establish a histological risk pattern that, complementary to the TNM classification, could have a predictive role in these early-stage tongue carcinomas.

Bisphosphonate-related osteonecrosis. Application of adipose-derived stem cells in an experimental murine model.

BACKGROUND: Bisphosphonate-related osteonecrosis of the jaw is a pathological condition without effective established treatment and preventive strategies. The aim of this study was to analyse the effect of adipose-derived stem cells (ASC) in an experimental murine model of osteonecrosis. MATERIAL AND METHODS: 38 Wistar rats were injected intraperitoneally with zoledronic acid. After treatment, upper jaw molars were extracted. The animals were randomly assigned to one of two groups. In the control group, saline solution was applied over the alveolar sockets after the tooth extractions. In the treatment group, ASCs were applied instead of saline solution. The control and treatment groups were subdivided based on the time of euthanasia. A clinical and histological analysis was performed. RESULTS: The presence of osteonecrosis in alveolar bone was observed in a similar distribution in both groups. In the ASC-treated group, new bone formation was greater than in controls. CONCLUSION: In this study, application of ASCs showed greater new bone formation in an osteonecrosis-like murine model. Previous inhibited post-extraction bone remodelling could be reactivated, and these findings appeared to be secondary to implantation of ASCs.

Benign notochordal cell tumors. / Tumor benigno de células notocordales.

Benign notochordal cell tumors (TBCN) are lesions with notochordal differentiation which affect the axial skeleton. They are characterized by asymptomatic or non-specific symptomatology and are radiologically unnoticed because of their small size, or because they are mistaken with other benign bone lesions, such as vertebral hemangiomas. When they are large, or symptomatic, can be differential diagnosis with metastases, primary bone tumors and chordomas. We present a case of a TBCN in a 50-year-old woman, with a sacral lesion seen in MRI. A CT-guided biopsy was scheduled to analyze the lesion, finding that the tumor was not clearly recognizable on CT, so the anatomical references of MRI were used to select the appropriate plane. The planning of the approach and the radio-pathological correlation were determinant to reach the definitive diagnosis.

TLR9 re-expression in cancer cells extends the S-phase and stabilizes p16(INK4a) protein expression.

Toll-like receptor 9 (TLR9) recognizes bacterial, viral or cell damage-associated DNA, which initiates innate immune responses. We have previously shown that TLR9 expression is downregulated in several viral induced cancers including HPV16-induced cervical neoplasia. Findings supported that downregulation of TLR9 expression is involved in loss of anti-viral innate immunity allowing an efficient viral replication. Here we investigated the role of TLR9 in altering the growth of transformed epithelial cells. Re-introducing TLR9 under the control of an exogenous promoter in cervical or head and neck cancer patient-derived cells reduced cell proliferation, colony formation and prevented independent growth of cells under soft agar. Neither TLR3, 7, nor the TLR adapter protein MyD88 expression had any effect on cell proliferation, indicating that TLR9 has a unique role in controlling cell growth. The reduction of cell growth was not due to apoptosis or necrosis, yet we observed that cells expressing TLR9 were slower in entering the S-phase of the cell cycle. Microarray-based gene expression profiling analysis highlighted a strong interferon (IFN) signature in TLR9-expressing head and neck cancer cells, with an increase in IFN-type I and IL-29 expression (IFN-type III), yet neither IFN-type I nor IL-29 production was responsible for the block in cell growth. We observed that the protein half-life of p16(INK4a) was increased in TLR9-expressing cells. Taken together, these data show for the first time that TLR9 affects the cell cycle by regulating p16(INK4a) post-translational modifications and highlights the role of TLR9 in the events that lead to carcinogenesis.

Histological study of the extratympanic portion of the discomallear ligament in adult humans: a functional hypothesis.

This study was carried out on histological aspects of the extratympanic portion of the discomallear ligament (DL) in adult humans. The temporomandibular joint (TMJ) was dissected bilaterally in 20 cadavers; in 15 cases the articular disc (AD) and the retroarticular tissue were extirpated. The extratympanic portion of the DL had the shape of a base-down triangle, in relation to the AD, and an upper vertex, in relation to the petrotympanic fissure. In five cases, the base, measured bilaterally, had an average length of 6.4 mm, while the distance from the base to the upper vertex averaged 9.3 mm in length. The extratypanic portion of the DL is an intrinsic ligament of the TMJ, composed of collagen fibres and abundant elastic fibres. We propose that this ligament could act as a tensor of the synovial membrane in movements of the TMJ.