A trespasser from a foreign land? A case report of primary mucosal leishmaniasis.

BACKGROUND: We report a clinically challenging and unusual case of L. donovani oral mucosal leishmaniasis. CASE PRESENTATION: Israeli resident with a former travel to central and North Africa, with no documented or prior cutaneous lesions presented with oral lesions of the maxillary gingiva and the upper lip. A delay in diagnosis and treatment have led to progression of the maxillary gingival lesions towards the hard palatal and the soft palate that could have potentially compromised the upper airway. CONCLUSIONS: This case highlights the importance of early diagnosis of leishmaniasis in patients with oral lesions and the laboratory workup necessary to appropriately characterize and treat the disease.

Acrofacial necrotic ulcers in an infant: An undiagnosed presentation.

Acral necrotic ulcers in infancy are rare but have been described in type I interferonopathies. Herein, we present a case of an 8-year-old child who presented at the age of one month with severe ulceronecrotic lesions on the face and limbs with exacerbations following exposure to cold weather. Despite extensive investigation the case remains undiagnosed to this day. We hypothesize that this case represents a novel and yet unknown autoinflammatory disease.

Salivary Gland Heterotopia, a Clinical and Pathological TNM Staging Challenge - Carcinoma ex Pleomorphic Adenoma Arising in a Parotid Lymph node.

INTRODUCTION: Heterotopia is the presence of a particular tissue / tumor at a non-physiological / ectopic site. The study primary goals: To review the current data investigating heterotopic, normal appearing, and diseased salivary gland tumors, in lymph nodes. To describe the meticulous pathological investigation and multidisciplinary decision-making process of a heterotopic carcinoma ex pleomorphic adenoma arising in an intra-parotid lymph node. MATERIALS AND METHODS: A literature search in the "PubMed" database using key words "carcinoma ex pleomorphic adenoma", "parotid lymph node", "salivary gland" and "heterotopia" was conducted. We describe the thorough pathological investigation and clinical decision-making process, focusing TNM staging system limitations. RESULTS: A few case reports presented either normal appearing salivary tissue, benign tumors or low and high-grade salivary malignancies arising in lymph nodes. We present the investigation, controversies and treatment decision process of a 46-year-old man with CXPA in intra-parotid lymph node. CONCLUSIONS: The staging scheme does not distinguish between nodal spread and primary tumor arising in a lymph node. Multidisciplinary input regarding prognosis and follow-up plans, may consider heterotopia differently from the usual pattern of nodal spread.

Oral white lesion in patients post-hematopoietic stem cell transplantation: a case series demonstrating the diagnostic dilemma.

The current National Institutes of Health (NIH) consensus paper excluded "white hyperkeratotic plaque" from the diagnostic criteria for oral chronic graft-versus-host disease (cGVHD) in order to ensure malignant transformation is not overlooked. Therefore, an isolated oral white plaque is recommended to be subjected to biopsy and pathologic examination. The cases described in this paper shed a new light on the clinical approach to oral white plaque post-hematopoietic stem cell transplantation. The objectives of this article are to demonstrate that a white plaque does not contradict a diagnosis of oral cGVHD, and to highlight the clinical considerations for taking a biopsy.

Spatial Intratumoral Heterogeneity Expression of PD-L1 Antigen in Head and Neck Squamous Cell Carcinoma.

INTRODUCTION: Immune-checkpoint inhibitors have demonstrated a significant survival benefit in metastatic and non-resectable head and neck squamous cell carcinoma (HNSCC). Patients with a combined positivity score (CPS) of 20 and higher benefit the most from therapy. Inaccurate definition of the CPS category might lead to the incorrect stratification of patients to immunotherapy. This study's main aim was to investigate programmed death-ligand 1 (PD-L1) antigen expression in HNSCC in diverse clinical situations and histological settings. MATERIALS AND METHODS: This is a prospective cohort study conducted in a tertiary referral medical center. Tissues were investigated for PD-L1 expression using the FDA-approved 22C3 immunohistochemistry assay (Dako). We analyzed potential associations between the CPS category and meaningful demographic, clinical, and outcome metrics. Furthermore, we investigated morphologically separate sites for CPS scores in whole surgical tissue specimens and matched preoperative biopsies. RESULTS: We analyzed 36 patients, of whom 26 had oral cavity SCC and 10 had laryngeal SCC. The overall, disease-specific, and progression-free survival of the HNSCC group of patients were not associated with the CPS category (p = 0.45, p = 0.31, and p = 0.88, respectively). There was a significant (18%, 95% CI 0.65-0.9) inconsistency between the CPS category determined in biopsies versus whole carcinoma analyses. We also found an uneven distribution of whole-tumor CPS attributed to spatial carcinoma invasiveness, tumor differentiation, and inflammatory cell infiltration heterogeneity. DISCUSSION AND CONCLUSIONS: Our data suggest that careful selection of tumor area for CPS analysis is important. PD-L1 antigen expression, clinically represented by CPS, may be up- or down-categorized in different clinical and pathological circumstances. The high whole-tissue CPS category scatter may clinically result in potential treatment modifications. We argue that CPS analysis requires not only adequacy (at least 100 viable tumor cells), but also correct representation of the tumor microenvironment.

The potential of somatostatin receptor 2 as a novel therapeutic target in salivary gland malignant tumors.

BACKGROUND: Treatment regimens for patients with metastatic or recurrent post-radiation, locoregional, unresectable salivary cancer are limited. An inverse correlation between somatostatin receptor 2 (SSTR2) and the proliferating marker Ki-67 in neuroendocrine tumors has enabled a treatment plan for metastatic disease, utilizing peptide receptor radionuclide therapy. Interestingly, healthy salivary glands express high levels of SSTR2. In this study, the presence of SSTR2, its correlation with Ki-67 in glandular salivary carcinomas and the clinical applicability thereof was determined. METHODS: In the retrospective part of this study, 76 adequate tumor tissue specimens obtained from patients diagnosed with primary or metastatic salivary carcinomas between 1988 and 2016, were collected for tissue array and histologically classified. Immunohistochemistry was performed to determine the presence, relative expression and potential correlation of SSTR2 and Ki-67. The clinical significance of SSTR2 expression was determined by prospectively assessing 68Ga-DOTATATE uptake using PET-CT imaging, in patients diagnosed with metastatic salivary gland malignant tumors between 2015 and 2016. RESULTS: Sixty-three primary cancer tumors and 14 metastatic tumors were tested. All tumor subtypes were found to express SSTR2 to some extent. The highest expression was seen in Mucoepidermoid carcinoma (MEC) tissues where the majority of specimens (86.4%) expressed SSTR2. A relatively strong immunohistochemical staining score for SSTR2 was observed in MEC, adenoid cystic carcinoma and polymorphous adenocarcinoma. Interestingly, an inverse correlation between SSTR2 and Ki-67 expressions was observed (44%) in MEC tissue. Uptake of 68Ga-DOTATATE was visualized using PET-CT imaging in 40% of patients, across metastatic MEC and ACC. All observations were found to be statistically significant. CONCLUSION: This study confirms the expression of SSTR2 in glandular salivary carcinomas and an inverse correlation in expression levels between SSTR2 and Ki-67. This lays a foundation for novel treatment options in salivary metastatic cancers where SSTR2 may be a potential novel therapeutic target.

Chronic expression of p16INK4a in the epidermis induces Wnt-mediated hyperplasia and promotes tumor initiation.

p16INK4a (CDKN2A) is a central tumor suppressor, which induces cell-cycle arrest and senescence. Cells expressing p16INK4a accumulate in aging tissues and appear in premalignant lesions, yet their physiologic effects are poorly understood. We found that prolonged expression of transgenic p16INK4a in the mouse epidermis induces hyperplasia and dysplasia, involving high proliferation rates of keratinocytes not expressing the transgene. Continuous p16INK4a expression increases the number of epidermal papillomas formed after carcinogen treatment. Wnt-pathway ligands and targets are activated upon prolonged p16INK4a expression, and Wnt inhibition suppresses p16INK4a-induced hyperplasia. Senolytic treatment reduces p16INK4a-expressing cell numbers, and inhibits Wnt activation and hyperplasia. In human actinic keratosis, a precursor of squamous cell carcinoma, p16INK4a-expressing cells are found adjacent to dividing cells, consistent with paracrine interaction. These findings reveal that chronic p16INK4a expression is sufficient to induce hyperplasia through Wnt-mediated paracrine stimulation, and suggest that this tumor suppressor can promote early premalignant epidermal lesion formation.

Subcutaneous granuloma annulare mimicking dermatomyositis.

We present three children who presented with papules and plaques over the knuckles, mimicking Gottron's papules of juvenile dermatomyositis, as well as subcutaneous nodules over the joints of the extremities that were initially thought to represent calcinosis cutis. However, thorough clinical and laboratory evaluation, as well as imaging, failed to support this diagnosis. Skin biopsies were consistent with a diagnosis of subcutaneous granuloma annulare. This unique phenotype of granuloma annulare should be recognized in order to prevent erroneous diagnosis and treatment.

Ameloblastoma incidentally detected in cone-beam computed tomography sialography: A case report and review of the literature.

BACKGROUND AND OVERVIEW: Cone-beam computerized tomographic (CBCT) imaging is increasingly used in the maxillofacial region for various purposes. The volumetric dataset created by means of CBCT increases the possibility of detecting incidental findings. CASE DESCRIPTION: In this case report, the authors describe an otherwise healthy 45-year-old man who was referred from the Sjogren's Syndrome Center in Jerusalem, Israel, for bilateral parotid CBCT sialographic imaging owing to xerostomia lasting for 4 months. CBCT sialographic imaging using iodine contrast material showed normal glandular structure and activity according to the postcannulation panoramic imaging. CBCT sialographic imaging routine volume interpretation revealed a lesion in the mandibular area causing destruction and perforation of the cortical plates, partial disappearance of adjacent lamina dura, and resorption of adjacent teeth, suggesting an aggressive benign tumor. Histopathologic examination confirmed mural cystic ameloblastoma, which was resected with preservation of the mental nerve and the lower mandibular border. The patient received bone graft and implants, with regular follow-ups and no recurrence after 4 years. CONCLUSIONS AND PRACTICAL IMPLICATIONS: This case strengthens the need for thorough examination of the whole CBCT imaging volume within and outside the region of interest to detect incidental findings with clinical importance.

Cutaneous Chronic Graft Versus Host Disease Following Allogeneic Haematopoietic Stem Cell Transplantation in Children: A Retrospective Study.

Chronic graft versus host disease (cGVHD) is a complication of allogeneic haematopoietic stem cell transplantation (HSCT). The aim of this study was to clinically characterize childhood cutaneous cGVHD. A retrospective study of children treated with HSCT at 2 tertiary medical centres in Israel between 2011 and 2014 was performed. A total of 112 children were included. Cutaneous cGVHD developed in 18% of subjects. Risk factors were older age, HSCT from peripheral blood and acute lymphoblastic leukaemia. The eruption was lichenoid in 90% of subjects, of whom one-third progressed to sclerosis. Topical treatments were usually sufficient in localized disease. Widespread eruption necessitated phototherapy, extracorporeal photopheresis and/or systemic immunosuppressants. Patients presenting with palmoplantar keratoderma, developed sclerosis. To the best of our knowledge, this is the first study describing childhood cutaneous cGVHD. Lichenoid eruption is the most common cutaneous pattern of cGVHD in children. Sclerotic changes may be associated with prior keratoderma. cGVHD poses a therapeutic challenge and better treatments should be sought.