Recommendations for the use of biomarkers for head and neck cancer, including salivary gland tumours: A Consensus of the Spanish Society of Medical Oncology and the Spanish Society of Pathology.

The treatment of head and neck and salivary gland tumours is complicated and is constantly evolving. Prognostic and predictive indicators of response to treatment are enormously valuable for designing individualized therapies, which justifies their research and validation. Some biomarkers, such as p16, Epstein-Barr virus, PD-L1, androgen receptors and HER-2, are already used routinely in clinical practice. These biomarkers, along with other markers that are currently under development, and the massively parallel sequencing of genes, ensure future advances in the treatment of these neoplasms. In this consensus, a group of experts in the diagnosis and treatment of tumours of the head and neck and salivary glands were selected by the Spanish Society of Pathology (Sociedad Española de Anatomía Patológica - SEAP) and the Spanish Society of Medical Oncology (Sociedad Española de Oncología Médica - SEOM) to evaluate the currently available information and propose a series of recommendations to optimize the determination and daily clinical use of biomarkers.

Recommendations for the use of biomarkers for head and neck cancer, including salivary gland tumours: A Consensus of the Spanish Society of Medical Oncology and the Spanish Society of Pathology / Recomendaciones para el uso de biomarcadores para cáncer de cabeza y cuello, incluyendo tumores de glándulas salivares: consenso de la Sociedad Española de Oncología Médica y la Sociedad Española de Patología

The treatment of head and neck and salivary gland tumours is complicated and is constantly evolving. Prognostic and predictive indicators of response to treatment are enormously valuable for designing individualized therapies, which justifies their research and validation. Some biomarkers, such as p16, Epstein–Barr virus, PD-L1, androgen receptors and HER-2, are already used routinely in clinical practice. These biomarkers, along with other markers that are currently under development, and the massively parallel sequencing of genes, ensure future advances in the treatment of these neoplasms.In this consensus, a group of experts in the diagnosis and treatment of tumours of the head and neck and salivary glands were selected by the Spanish Society of Pathology (Sociedad Española de Anatomía Patológica – SEAP) and the Spanish Society of Medical Oncology (Sociedad Española de Oncología Médica – SEOM) to evaluate the currently available information and propose a series of recommendations to optimize the determination and daily clinical use of biomarkers.(AU)

El tratamiento de los tumores de cabeza y cuello y de glándulas salivales es complejo, y evoluciona de forma constante. Los indicadores pronósticos y predictivos de respuesta al tratamiento son enormemente valiosos para diseñar terapias individualizadas, lo que justifica su investigación y validación. Algunos biomarcadores como p16, el virus de Epstein-Barr, PD-L1, los receptores de andrógenos o HER-2, ya se utilizan de manera rutinaria en la práctica clínica. Estos biomarcadores, junto con otros marcadores que están actualmente en desarrollo, y la secuenciación masiva de genes, aseguran los futuros avances en el tratamiento de estas neoplasias. En este consenso, un grupo de expertos en el diagnóstico y tratamiento de los tumores de cabeza y cuello y glándulas salivales seleccionado por la Sociedad Española de Anatomía Patológica (SEAP) y la Sociedad Española de Oncología Médica (SEOM) evalúan la información actualmente disponible y proponen una serie de recomendaciones para optimizar la determinación y utilización en la práctica clínica diaria de los biomarcadores.(AU)

Diagnostic role of DOG-1, GFAP and B-catenin in Basal cell Adenoma and Cellular Pleomorphic Adenoma of the Salivary Gland.

BACKGROUND: Pleomorphic Adenoma (PA) and Basal cell adenoma (BCA) are benign salivary gland tumors that may pose a diagnostic challenge if typical features are not present. Due to the increased relapse and malignant transformation rate of the former, a correct diagnosis carries relevant prognostic information. Even though immunohistochemistry (IHC) plays a limited role in the diagnosis of these tumors, the use of IHC panels could increase diagnostic accuracy. In the present work, we aimed to demonstrate that the use of an IHC panel consisting of Glial Fibrillary Acid Protein (GFAP), B-Catenin and Discovered On GIST 1 (DOG-1) can aid in the differential diagnosis between PA and BCA. METHODS: We analyzed 18 cases of benign salivary gland tumors (Pleomorphic adenomas and Basal cell adenomas) with overlapping histologic features. First, a head and neck pathologist diagnosed the cases relying on morphology alone. Afterwards, cases were re-evaluated considering the IHC panel results. Inter-observer IHC scoring concordance was evaluated with pre-defined marker cut-off points using Cohen's Kappa scores. RESULTS: Based on morphology alone, 9 cases were classified as PA while the remaining tumors were considered to be BCA. Five out of nine BCA cases showed GFAP staining and absent nuclear B-catenin and DOG-1 positivity. Conversely, 2 PA cases showed absent GFAP and positive nuclear B-catenin with concurrent DOG-1 expression. Therefore, after IHC evaluation, up to 40% of morphologic diagnoses were reconsidered. Overall, the inter-observer concordance for IHC evaluation was good (resulting Kappa Scores between 0.78 and 1). CONCLUSION: Our work supports the use of a concise IHC panel to improve the diagnostic accuracy of benign salivary gland tumors with overlapping histologic features.

Recommendations for the use of biomarkers for head and neck cancer, including salivary gland tumours: a consensus of the Spanish Society of Medical Oncology and the Spanish Society of Pathology.

The treatment of head and neck and salivary gland tumours is complicated and evolves constantly. Prognostic and predictive indicators of response to treatment are enormously valuable for designing individualized therapies, which justifies their research and validation. Some biomarkers, such as p16, Epstein-Barr virus, PD-L1, androgen receptors and HER-2, are already used routinely in clinical practice. These biomarkers, along with other markers that are currently under development, and the massively parallel sequencing of genes, ensure future advances in the treatment of these neoplasms. In this consensus, a group of experts in the diagnosis and treatment of tumours of the head and neck and salivary glands were selected by the Spanish Society of Pathology (Sociedad Española de Anatomía Patológica-SEAP) and the Spanish Society of Medical Oncology (Sociedad Española de Oncología Médica-SEOM) to evaluate the currently available information and propose a series of recommendations to optimize the determination and daily clinical use of biomarkers.

Cardiac involvement in Adult Multisystemic Inflammatory Syndrome related to COVID-19. Two case reports.

In this article we describe two cases that presented with persistent fever and a hyperinflammatory state in association with severe acute respiratory syndrome-coronavirus-2 infection with various negative reverse transcription-polymerase chain reaction results. These cases subsequently developed myocarditis with cardiogenic shock that required vasoactive drugs and had a good response to corticosteroid treatment. All cases met criteria for a definitive case of multisystemic inflammatory syndrome in adults, a recently described entity associated with coronavirus disease 2019, which has a good response to immunomodulators and a good prognosis in most cases. .

A tree-based machine learning model to approach morphologic assessment of malignant salivary gland tumors.

Malignant salivary gland tumors represent a challenge for pathologists due to their low frequency and morphologic overlap. In recent years machine learning techniques have been applied to the field of pathology to improve diagnostic performance. In the present work, we fitted a machine learning algorithm to approach the diagnosis of malignant salivary gland tumors. Twelve morphologic variables were scored across 115 samples representing the most commonly encountered malignant salivary gland tumors. The sample was randomly split into a discovery and validation set. A recursive partitioning algorithm was used to systematically screen and organize candidate variables into a classification tree using the discovery set. A cross-validation strategy was used to tune the algorithm hyperparameters. Inter-observer concordance was calculated by independent evaluation of 26 randomly selected cases. The five-tiered tree built, required the evaluation of 6 morphological variables. Basaloid appearance, presence of mucous cells, necrosis, cribriform pattern, clear cells and keratinization were selected by the algorithm to build the tree. This diagnostic tool correctly classified 89.9% and 84.6% of the samples in the discovery and validation sets respectively. Misclassification pattern was consistent between both sets. Misclassified tumors belonged to one of three histologic types: epithelial-myoepithelial, polymorphous and mucoepidermoid carcinomas. Other histotypes demonstrated perfect recall in both the discovery and validation sets. Overall inter-observer concordance was good, with median kappa scores between the expert evaluator and training pathologists being 0.81. Overall, our classification tool developed using a recursive partitioning algorithm can effectively guide the morphological approach to malignant salivary gland tumors.

Fibrovascular Tumor-Like Lesions of the Facial Nerve.

BACKGROUND: Facial nerve tumors (FNTs) are relatively rare benign lesions that arise from any segment of the facial nerve (FN). About half of all patients present with FN dysfunction, mainly long-standing or progressive facial paralysis. Diagnosis of an FNT is usually based on radiological imaging and confirmed by histological study. Most reported cases of FNTs are schwannomas and hemangiomas. OBJECTIVES: The aim of this study was to review 4 cases of lesions with clinical, radiological, and surgical findings that suggested an FNT, the pathology revealing a fibrovascular proliferation with no clear signs of a specific tumor. METHOD: Medical records of patients who had surgery due to an FN lesion were reviewed. Cases with known tumoral lesions were excluded. Four patients with tumor-like lesions were identified. Their imaging studies were re-evaluated. The pathological study included hematoxylin-eosin, Masson's trichrome, and immunohistochemistry for S100 protein, neurofilaments, CD31, Wilms' tumor 1 (WT1), and D240. RESULTS: The 4 cases revealed tumor-like fibrovascular lesions that could not be classified as typical pathological entities. All cases had a complete facial palsy preoperatively. Computed tomography and magnetic resonance imaging (MRI) suggested schwannoma or hemangioma. A complete excision was achieved, and a facial reconstruction was performed immediately after interruption. Postoperative FN function was improved in all cases. The histological study showed nervous tracts of normal morphology, with fibrous and vascular tissue interspersed in variable proportions. All cases showed areas of fibrosis with Masson's stain. In all cases, nervous tissue and Schwann cells tested positively for neurofilaments and S100, respectively. In vascular areas, endothelial cells stained positively for CD31, and negatively for D240 and WT1. CONCLUSIONS: Fibrovascular lesions of the FN may mimic primary FNTs, especially schwannomas and hemangiomas. Surgical excision with grafting or nerve transfer is the procedure of choice if a complete facial paralysis is found. This unusual condition should be considered when counseling patients with FN lesions. The lack of hyperintensity on MRI T2-weighted images may suggest the presence of fibrous tissue.

Metastatic neuroblastoma mimicking an infantile hemangioma.

Neuroblastoma is the most common solid tumor malignancy in the first year of life. We present a rare case of a 5-month-old girl with an infraorbital tumor that simulated an infantile hemangioma clinically but was ultimately diagnosed as metastatic neuroblastoma.

Oseltamivir-induced toxic epidermal necrolysis in a patient with Cushing's disease.

We report a case of a patient with Cushing's disease with oseltamivir-induced toxic epidermal necrolysis, who was treated with cyclosporine with favorable evolution. There is only one case reported of Cushing's disease and toxic epidermal necrolysis and very few oseltamivir-induced toxic epidermal necrolysis cases in literature. This report also discusses the role that the preexisting hypercortisolism condition may have played in the development and favorable resolution of the toxic epidermal necrolysis.

Orbital Radioiodine Uptake on Scintigraphy in a Patient with Thyroid Cancer.

Background: Orbital radioiodine uptake in patients with thyroid cancer is very uncommon with only a few reported cases, most of them being metastasis. The accumulation of 131I in nonthyroidal tissues and body fluids can lead to false-positive results in scintigraphy, which are sometimes difficult to differentiate from true metastases. Case Report: A post-therapy 131I whole-body (WBI) scintigraphy in an asymptomatic 57-year-old female with papillary thyroid carcinoma (PTC) previously treated with total thyroidectomy and 6 ablative radioiodine doses showed a focal uptake in the right eyeball region. The lesion, placed in the orbital space, was surgically removed, and histology revealed a conjunctival inclusion cyst. Discussion: Ocular and orbital metastases from thyroid cancer, as well as some non-neoplastic disorders or contamination, are possible causes for 131I uptake in the orbital region in scintigraphy. Conjunctival inclusion cyst is a condition associated with incidental 131I uptake that had not been reported before and should be ruled out as a non-metastatic cause of orbital radioiodine uptake in patients with PTC.

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. Conclusions: 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

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Congenital tufted angioma: A multicenter retrospective study of 30 cases.

BACKGROUND: Recent reports indicate that tufted angioma is a rare vascular neoplasm that manifests more frequently at birth than previously thought. Few studies specifically address congenital presentation. OBJECTIVES: We analyzed the clinicopathological characteristics, clinical course, and treatment of congenital tufted angioma (cTA) and evaluated variables that were indicative of problematic lesions. METHODS: We performed an observational retrospective study of 30 patients with cTA in 9 Spanish hospitals over a 14-year period. Histopathology and immunohistochemistry studies were performed. RESULTS: Congenital tufted angioma mainly affected the limbs (56.67%), followed by the face and/or neck (23.33%). Almost three-quarters of facial cTA were located over the mandibular area. Immunohistochemically, proliferating cells expressed markers of endothelial cells, with some clusters of cells, especially at the periphery of the aggregates, showing positivity for podoplanin. As no associated complications were observed in 66.67% of cases, no treatment was started. LIMITATIONS: Data were collected retrospectively. CONCLUSIONS: Our findings emphasize the clinical features and course of cTA. The possibility of cTA should be considered when a poorly defined congenital infiltrative vascular tumor with(out) overlying hirsutism appears over the mandibular area. Location on the face and/or neck requires a more comprehensive workup, since potentially severe complications often appear early.

¿Cuál sería su tratamiento? / What would your treatment be?

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Hemangioma cavernoso frontal / Frontal cavernous hemangioma

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Fibrous dysplasia of the temporal bone secondary to ear surgery: a case report.

INTRODUCTION: In this report, we describe the clinical course, diagnostic features and management of a patient with fibrous dysplasia of the temporal bone 7 years after middle ear surgery on the same side. CASE PRESENTATION: A 16-year-old Caucasian girl presented to our hospital with a growing bone lesion in the roof of the left temporal bone. She had undergone a previous tympanoplasty at 7 years of age because of a cholesteatoma. At the time of that first surgery, no radiological or histological signs indicated a bone disorder. A computed tomographic scan of the temporal bone showed a lesion with rarefaction areas and lytic images inside that affected the roof of the cavity to the tegmen tympani without alterations in the inner ear. A surgical revision of the ear cavity was performed by resecting the lesion and regularizing the cavity. The histopathologic study confirmed fibrous dysplasia. The patient progressed satisfactorily after surgery with no evidence of recurrence. CONCLUSION: To the best of our knowledge, this is the first report of fibrous dysplasia of the temporal bone secondary to ear surgery.