Adenoid 'ameloblastoma': Clinicopathological description of 4 additional BRAF-negative cases.

OBJECTIVE: Adenoid ameloblastoma (AA) is an epithelial odontogenic tumor that was recognized as a separate entity in the last odontogenic classification of WHO in 2022. The etiology is unknown, and the pathogenesis remains controversial. The objective of this study is to contribute the clinicopathological features of 4 additional BRAF-negative cases to the existing literature, aiming to enhance the molecular understanding of this unique tumor in the forthcoming classification. MATERIALS AND METHODS: This study consists of a case series of four patients diagnosed with AA. The patients' demographic and clinical information were collected from the universities' medical achieves. Histopathologically, all cases were reexamined according to the latest update of the WHO odontogenic tumor classification. In addition to H&E and immunohistochemical stains, cytogenetics was also evaluated. RESULTS: Well-defined unilocular radiolucent lesions were observed in all cases. Ameloblastoma-like components exhibited reserved nuclear polarity, suprabasal stellate reticulum-like epithelium, duct-like structure, whorls/morules, and cribriform architecture were common features. Variable immunoreactivity to CK7, CK19, CK14, p63, and p40 were determined, and proliferative activity was greater than 15%. The BRAF molecular study revealed no mutations. CONCLUSIONS: When diagnosing AA, the essential histopathological characteristics must be rigorously applied, and a significant portion of the lesion should contain these features. Additionally, despite limited molecular data, since the BRAF mutation commonly observed in ameloblastomas is not present in the majority of AA cases, we propose changing the term "ameloblastoma" to "ameloblastic" and referring to it as "adenoid ameloblastic tumor" in the forthcoming classification.

Juvenile Xanthogranuloma Presented with Buphthalmos and Corneal Clouding in Neonatal Period: A Case Report.

Aim: To report an ocular juvenile xanthogranuloma (JXG) case presented with buphthalmos, corneal cloudiness, and normal intraocular pressure (IOP) in the neonatal period and treated with Ahmed glaucoma valve (AGV) implantation. Background: JXG is a rare disorder predominantly seen in infants, but the neonatal presentation is extraordinary. Although spontaneous hyphema is a common presenting sign in JXG, buphthalmos and corneal opacity in the neonatal period were reported only in one case, which had high IOP values at presentation. Case presentation: Sixteen-day-old male patient presented with buphthalmos, diffuse corneal clouding, and 11 mm Hg of IOP value in the right eye. IOP increased to 28 mm Hg three weeks later, and spontaneous hyphema developed, which did not respond to antiglaucomatous medications and topical corticosteroids. AGV was implanted, and the IOP decreased to 13 mm Hg postoperatively. In the follow-ups, numerous firm yellowish nodules were noticed on the patient's skin during the examination under general anesthesia. Histopathological examination of the skin nodules was compatible with the diagnosis of JXG. Lens subluxation and phacodonesis were developed during the follow-up and were managed with pars plana lensectomy. After a silent period of 3 months, epithelial ingrowth was determined around the side port entrance. Unfortunately, the ingrowth did not respond to cryotherapy and resulted in phthisis bulbi. Pathological evaluation of the enucleated phthisic eye revealed posterior segment involvement. Conclusion: Ocular JXG can be present with buphthalmos, corneal opacity, and normal IOP values without any skin lesions in the neonatal period. Neonatal presentation of JXG may be associated with limited medical therapy response and aggressive disease course. Clinical significance: This case report introduces the second ocular JXG case, which presented with buphthalmos and corneal cloudiness, and the third pathologically proven posterior segment involvement of JXG in the literature. How to cite this article: Dericioglu V, Sevik MO, Eraslan M, et al. Juvenile Xanthogranuloma Presented with Buphthalmos and Corneal Clouding in Neonatal Period: A Case Report. J Curr Glaucoma Pract 2022;16(2):128-131.

Low Density Granulocytes and Dysregulated Neutrophils Driving Autoinflammatory Manifestations in NEMO Deficiency.

NF-κB essential modulator (NEMO, IKK-γ) deficiency is a rare combined immunodeficiency caused by mutations in the IKBKG gene. Conventionally, patients are afflicted with life threatening recurrent microbial infections. Paradoxically, the spectrum of clinical manifestations includes severe inflammatory disorders. The mechanisms leading to autoinflammation in NEMO deficiency are currently unknown. Herein, we sought to investigate the underlying mechanisms of clinical autoinflammatory manifestations in a 12-years old male NEMO deficiency (EDA-ID, OMIM #300,291) patient by comparing the immune profile of the patient before and after hematopoietic stem cell transplantation (HSCT). Response to NF-kB activators were measured by cytokine ELISA. Neutrophil and low-density granulocyte (LDG) populations were analyzed by flow cytometry. Peripheral blood mononuclear cells (PBMC) transcriptome before and after HSCT and transcriptome of sorted normal-density neutrophils and LDGs were determined using the NanoString nCounter gene expression panels. ISG15 expression and protein ISGylation was based on Immunoblotting. Consistent with the immune deficiency, PBMCs of the patient were unresponsive to toll-like and T cell receptor-activators. Paradoxically, LDGs comprised 35% of patient PBMCs and elevated expression of genes such as MMP9, LTF, and LCN2 in the granulocytic lineage, high levels of IP-10 in the patient's plasma, spontaneous ISG15 expression and protein ISGylation indicative of a spontaneous type I interferon (IFN) signature were observed, all of which normalized after HSCT. Collectively, our results suggest that type I IFN signature observed in the patient, dysregulated LDGs and spontaneously activated neutrophils, potentially contribute to tissue damage in NEMO deficiency.

Histopathological Review of Diagnostic Categories of the Milan System for Reporting Salivary Gland Cytopathology - An Institutional Experience of 6 Years.

INTRODUCTION: Salivary gland malignancies account for 2 to 4% of head and neck cancers. Fine needle aspiration cytology (FNAC) is used in preoperative diagnosis of salivary gland lesions. Although FNAC is a highly reliable technique for preoperative diagnosis, there were no consensus on salivary gland cytopathology reporting. Recently, an international group has recommended a classification system for salivary gland FNAC reporting titled "Milan System for Reporting Salivary Gland Cytopathology" (MSRSGC). In this study, we aimed to evaluate the usability of the Milan System, its ability to determine the risk of malignancy for each category, with comparisons of inital cytologic and final histopathological diagnosis. MATERIALS AND METHODS: We performed a retrospective analysis of salivary gland lesion FNAC in our department from 2013 to 2019. A total of 578 FNACs were performed in 514 patients. Of these, 85 cases had surgical follow-up (parotid gland, n = 73, submandibular gland, n = 12). The cytological samples were categorized according to the MSRSGC into six categories by two pathologists. The risk of malignancy (ROM) and diagnostic accuracy values were calculated for each diagnostic categories. RESULTS: A total of 85 aspirates of the patients with follow-up, the MSRSGC diagnostic categories were as follows: non-diagnostic in 7 aspirates (8.2%), non-neoplastic in 3 (3.5%), atypia of undetermined significance (AUS) in 9 (10.5%), benign neoplasm in 43 (50.5%), salivary gland neoplasm of undetermined malignant potential in 7 (8.2%), suspicious for malignancy in 10 (11.7%), and malignant in 6 (7%). The ROM for each category was 28, 5%, 0%, 33%, 0%, 28.5%, 90%, and 100%, respectively. CONCLUSION: FNAC plays a critical role in the evaluation of patients with salivary gland lesions. The MSRSGC helps in the standardization of the process of diagnosis and clinical management of salivary gland lesions, especially of AUS and SUMP categories that are indeterminate categories in nature.

Ischemic Preconditioning and Iloprost Reduces Ischemia-Reperfusion Injury in Jejunal Flaps: An Animal Model.

BACKGROUND: Free jejunal flaps are among the most commonly used flaps for esophageal reconstruction. However, ischemia-reperfusion injury caused by warm ischemia seen during transfer limits their use. Iloprost, a prostacyclin analogue, has been shown to reduce ischemia-reperfusion injury in various organs. The authors investigated tissue damage in jejunal flaps with iloprost and ischemic preconditioning and compared the effectiveness of these two modalities. METHODS: Thirty-four Sprague-Dawley rats were randomized into five groups: sham, ischemia-reperfusion (control), ischemic preconditioning, iloprost, and ischemic preconditioning plus iloprost. All flaps, except those in the sham group, underwent ischemia for 60 minutes and reperfusion for 2 hours. Flap perfusion was assessed by laser Doppler perfusion monitoring. Histologic sections were scored using the Chiu scoring system. Superoxide dismutase and myeloperoxidase levels were measured spectrophotometrically. RESULTS: Animals that were administered iloprost and/or underwent ischemic preconditioning had better postischemic recovery of mesenteric perfusion (ischemic preconditioning, 78 percent; iloprost, 83 percent; ischemic preconditioning plus iloprost, 90 percent; versus ischemia-reperfusion, 50 percent; p < 0.05). All intervention groups showed improved histology of jejunal flaps following ischemia-reperfusion injury (ischemic preconditioning, 3; iloprost, 2.3; ischemic preconditioning plus iloprost, 3.2; versus ischemia-reperfusion, 4.7; p < 0.01, p < 0.001, and p < 0.05, respectively). Superoxide dismutase levels were higher in ischemic preconditioning, iloprost plus ischemic preconditioning, and iloprost groups (ischemic preconditioning, 2.7 ± 0.2; ischemic preconditioning plus iloprost, 2.5 ± 0.3; versus ischemia-reperfusion, 1.2 ± 0.1; p < 0.01; iloprost, 2.4 ± 1.1; versus ischemia-reperfusion, 1.2 ± 0.1; p < 0.05). Myeloperoxidase, a marker for neutrophil infiltration, was lower in the iloprost group (iloprost, 222 ± 5; versus ischemia-reperfusion, 291 ± 25; p < 0.05). CONCLUSIONS: This study showed that both iloprost and ischemic preconditioning reduced reperfusion injury in jejunal flaps. Based on histologic results, iloprost may be a novel treatment alternative to ischemic preconditioning.

A new immunohistochemical marker, insulinoma-associated protein 1 (INSM1), for Merkel cell carcinoma: Evaluation of 24 cases.

Merkel cell carcinoma (MCC) is an uncommon primary neuroendocrine carcinoma of the skin. Nowadays, pathologists are required to perform immunohistochemistry to demonstrate neuroendocrine and epithelial differentiation for diagnosis of MCC. Insulinoma-associated protein 1 (INSM1) is a zinc-finger transcription factor expressed in tissues undergoing terminal neuroendocrine differentiation, and INSM1 immunohistochemistry is a well-validated nuclear marker of neuroendocrine differentiation. We evaluated 24 cases of MCC for the expression of INSM1 and compared it with frequently used neuroendocrine markers, Chromogranin A, Synaptophysin, and CD56. INSM1 was positive in all cases, and its expression was stronger, more extensive, clean and homogeneous compared to other markers. As a consequence, INSM1 can be used to serve as a solitary marker for neuroendocrine differentiation due to high sensitivity and specificity in MCC cases.

An unusual presentation of ocular rosacea.

Rosacea is a chronic, progressive disease of unknown cause affecting the eye and the facial skin. Ocular rosacea is often underdiagnosed if the ophthalmologist does not inspect the patient's face adequately during the ocular examination. Severe ocular complications and blindness can occur if the treatment is delayed because of non-diagnosis of the rosacea. Here, we present a case of ocular rosacea in a 78-year-old Caucasian woman. Based on the ocular lesions, which preceded cutaneous involvement, she was misdiagnosed as having ocular cicatricial pemphigoid initially. This case emphasizes the difficulty in diagnosis when ocular findings precede those of skin manifestations, and rosacea should be kept in mind in the differential diagnosis of chronic cicatrizing conjunctivitis.

An unusual presentation of ocular rosacea / Uma apresentação incomum da rosácea ocular

ABSTRACT Rosacea is a chronic, progressive disease of unknown cause affecting the eye and the facial skin. Ocular rosacea is often underdiagnosed if the ophthalmologist does not inspect the patient's face adequately during the ocular examination. Severe ocular complications and blindness can occur if the treatment is delayed because of non-diagnosis of the rosacea. Here, we present a case of ocular rosacea in a 78-year-old Caucasian woman. Based on the ocular lesions, which preceded cutaneous involvement, she was misdiagnosed as having ocular cicatricial pemphigoid initially. This case emphasizes the difficulty in diagnosis when ocular findings precede those of skin manifestations, and rosacea should be kept in mind in the differential diagnosis of chronic cicatrizing conjunctivitis.

RESUMO A rosácea é uma doença crônica e progressiva de causa desconhecida que afeta o olho e a pele do rosto. A rosácea ocular é muitas vezes pouco diagnosticada se o oftalmologista não inspecionar adequadamente o rosto do paciente durante o exame ocular. Podem ocorrer complicações oculares graves e cegueira se o tratamento for adiado devido ao não diagnóstico da rosácea. Um caso de rosácea ocular em uma mulher caucasiana de 78 anos de idade é apresentado. Com base nas lesões oculares, que precederam o envolvimento cutâneo, ela foi mal diagnosticada como penfigóide cicatricial ocular inicialmente. Este caso enfatiza a dificuldade de diagnóstico quando os achados oculares precedem aqueles das manifestações da pele e um diagnóstico de rosácea deve ser mantido em mente no diagnóstico diferencial da conjuntivite cicatrizante crônica.

Acquired progressive lymphangioma: Case report with partial response to imiquimod 5% cream.

Acquired progressive lymphangioma (APL), or benign lymphangioendothelioma, is an unusual entity derived from vascular structures. Clinically and histopathologically it may resemble Kaposi's sarcoma and well-differentiated angiosarcoma, causing a diagnostic problem. We report an individual with APL initially diagnosed with Kaposi's sarcoma who underwent unnecessary laboratory testing. Imiquimod 5% cream stopped the progression of the lesion. Awareness of this rare entity may prevent patients from undergoing excessive testing. Imiquimod may be used as a safe, effective treatment option.

Cutaneous Tuberculosis Occurring After a Skin Cut in a Child.

BACKGROUND: Tuberculosis is a common problem in Turkey, and cutaneous tuberculosis is a rare form of extrapulmonary tuberculosis. Herein, the authors describe a case of cutaneous tuberculosis (lupus vulgaris) occurring after contact with a sheep. CASE: A 15-year-old boy was admitted to Marmara University School of Medicine Pendik Training and Research Hospital (Istanbul, Turkey) with delayed wound healing on the left index finger and left axillary lymphadenopathy. His medical history was unremarkable except for a wound incurred when he slaughtered a sheep 3 months before. One month after this injury, the patient developed enlargement of the left axillary lymph node on the side of the wounded extremity, and the wound turned a dark black color. The biopsy specimens obtained from the wounded skin and lymph nodes showed granulomatous reaction, but acid-fast bacilli (AFB) could not be shown with Ehrlich-Ziehl Neelsen staining. The patient tested positive in an interferon-gamma release assay. Computerized tomography scans of the thorax were normal, and early morning gastric lavage specimen was negative for AFB. The wound and axillary lymphadenopathy disappeared after institution of anti-tuberculosis therapy. CONCLUSION: Tuberculosis infection must be considered in chronic skin lesions with granulomatous reaction occurring in countries with high prevalence of tuberculosis.

Calretinin immunohistochemistry for the diagnosis of Hirschprung disease in rectal biopsies.

In this study we aimed to evaluate the usability of calretinin staining in the diagnosis and exclusion of HD in 36 rectal biopsies. Through immunohistochemical examination, in of a total of 21 pediatric patients in whom ganglion cells were detected in first rectal biopsies and in re-biopsies, ganglion cells were seen through nuclear and cytoplasmic staining. In the lamina propria and superficial submucosa, staining of nerve fibers was detected in a granular pattern in varying intensities. Out of a total of 5 biopsies (including one re-biopsy) of non-HD patients, where ganglion cells could not be seen, the nerve fibers were all stained. On the other hand, in 10 HD patients, diagnosed by a colon pull through operation, calretinin staining was not detected in any area of the rectal biopsies except for the mast cells. We conclude that calretinin immunostaining for the diagnosis of HD is an easy and reliable method for use in daily practice.

Interobserver agreement among histological patterns and diagnosis in lung adenocarcinomas.

OBJECTIVE: The aim of this study was to investigate the interobserver agreement in determination of the dominant histological pattern and the final diagnosis in lung adenocarcinomas. MATERIAL AND METHOD: A total of 12 patients with a diagnosis of primary lung adenocarcinoma were included in the study. Twelve pathologists from eight study centers were asked first to determine the dominant histological pattern in these cases and then to decide whether the final diagnosis was in situ, minimally invasive or invasive adenocarcinoma. RESULTS: The kappa value for the agreement in determining the dominant pattern among the pathologists was 0.36 (p < 0.001), with the values for the lepidic, acinar, papillary, solid, micropapillary patterns and mucinous character of adenocarcinoma being 0.34, 0.28, 0.30, 0.80, 0.16 and 0.38 respectively (p < 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.001). None of the cases was diagnosed as in situ adenocarcinoma. On the other hand, the kappa value for the agreement in differentiating minimally invasive from invasive adenocarcinoma among reviewers was 0.17 (p < 0.001). CONCLUSION: The agreement among pathologists in determining the subtype of lung adenocarcinomas that depends on the identification of the dominant pattern was at intermediate level. In addition, the agreement in deciding whether the case is minimally invasive or invasive, was at low level. The criteria defining the histological patterns should be clarified and described in more detail. Educational activities and larger multicenter studies might be helpful in improving the agreement and standardization.

The correlation between reactive oxygen species and histopathology of the liver, gut, and kidneys in animals with elevated intra-abdominal pressure.

BACKGROUND: Clinical and experimental studies have shown that the laparoscopic procedure provides a typical model of ischemia-reperfusion injury in the organs by oxygen-derived free radicals. A pneumoperitoneum produces ischemia during insufflation and reperfusion during desufflation. The aim of this study was to assess the causative role of free radical-mediated reactions in tissue damage under different intra-abdominal insufflation pressures. MATERIALS AND METHODS: Thirty five mature New Zealand white rabbits were assigned to three groups of 10 animals. In groups 1, 2, and 3, the designated pressures of 10, 15, and 20 mm Hg, respectively. The remaining 5 animals underwent laparotomy, using a 10-cm midline incision taken as group 4 (control). Blood samples were collected before (0 minutes) and at the end of the procedure (60 minutes). After the collection of the last blood samples, all animals were sacrificed and the samples from the liver, kidney, and gut were obtained for histologic evaluation and also measurements of tissue malondialdehyde (MDA) levels. RESULTS: The nitric oxide levels were not changed in groups 1 and 2, but increased significantly in group 3. Tissue MDA levels were significantly higher in groups 1 and 2 than groups 3 and 4. Histopathologic examination of the kidney revealed some findings of reversible hypoxic cell injury, including acute cellular swelling, vascular congestion, and some early findings of irreversible injury, such as lysis of the cytoplasmic membrane in all groups and focal parancymal bleeding area in only group 3 as a consequence of increased pressure. Liver histology revealed cellular swelling and karyorhexis in hepatocytes in group 1, whereas only congestion and sinusoidal dilatation was observed in groups 2 and 3. CONCLUSION: Our experimental study showed that abdominal insufflation causes ischemia and free radical production, which seems responsible for the cell damage that occured during laparoscopic surgery.

Effect of increased abdominal pressure on cytokines (IL1 beta, IL6, TNFalpha), C-reactive protein (CRP), free radicals (NO, MDA), and histology.

BACKGROUND: It is generally accepted that proinflammatory mediators, including cytokines, are responsible for the metabolic changes associated with injury. Recent clinical and experimental studies have also shown that the laparoscopic procedures actually produce ischemia-reperfusion injury in the organs by oxygen-derived free radicals. This study aimed to assess the effect of different insufflation pressures and laparotomy on tissue response by comparing the proinflammatory cytokines, C-reactive protein, and serum and tissue levels of oxygen-derived free radicals. METHODS: Forty mature New Zealand white rabbits were assigned to 4 groups of 10 animals. In groups 1 to 3, CO2 pneumoperitoneum was created using an automatic insufflator to the designated pressure of 10, 15, and 20 mm Hg, respectively. The remaining 10 animals underwent laparotomy using 10 cm midline incision (group 4). Blood samples were collected before (0 min) and at the end of the procedure (60 min). After the collection of last blood samples, all animals were killed and samples from liver and gut were obtained for measurements of tissue malondialdehyde levels and histology. RESULTS: The proinflammatory cytokine levels were increased significantly in groups 1 to 3, but did not change in the laparotomy group. Serum C-reactive protein levels were elevated in all groups. The comparison of the results between the laparotomy and laparoscopy groups showed that serum interleukin 6 and nitric oxide levels were significantly elevated in relation the intra-abdominal pressure, and serum interleukin 6 and nitric oxide levels peaked in group 3. Tissue malondialdehyde levels were significantly higher in groups 1 and 2 than in groups 3 and 4. CONCLUSIONS: The findings of our experiment suggest that the elevated intra-abdominal pressure is responsible for ischemia, free radical production, and proinflammatory cytokine response-mediated cell damage during laparoscopic surgery.

The association of mast cell density with myometrial invasion in endometrial carcinoma: a preliminary report.

It is known that cancer is not a single transformational event. It is rather a multistage process involving complex interactions with the surrounding cellular microenvironment. Mast cells accumulate at sites of tumor growth in response to numerous chemoattractants. Our aim was to investigate the relationship between mast cell density (MCD) and myometrial invasion in endometrial carcinomas. Immunohistochemistry was performed on 35 unselected consecutive hysterectomy specimens from patients with endometrial adenocarcinoma. C-kit-positive mast cell assessment was performed in the myometrium adjacent to tumor tissue. A mean number of or=16 mast cells was regarded as high mast cell density (H-MCD). A significant correlation (p=0.018, Pearson Chi-Square test) between H-MCD and the presence of myometrial invasion was demonstrated in endometrial carcinomas. H-MCD was found in 54% of all cases, and 94% of H-MCD cases had myometrial invasion, suggesting a role of mast cells or an interaction with tumor. Therapeutic modalities orientated to these cells or their microenvironment as a new target for adjuvant treatment might determine the prognosis in endometrial carcinomas.

Prognostic value of expression of p53, proliferating cell nuclear antigen, and c-erbB-2 in laryngeal carcinoma.

BACKGROUND: The molecular mechanisms in malignant transformation of laryngeal mucosa are unknown; many clinical and pathological factors affect prognosis. We investigated a possible correlation between overexpression of p53, proliferating cell nuclear antigen (PCNA), and c-erbB-2, and the clinicopathologic features of laryngeal squamous cell carcinoma (SCC) and clarify their prognostic value. MATERIAL/METHODS: Thirty-three men with laryngeal SCC participated; all underwent primary surgery or surgery plus radiotherapy between 1999 and 2004 at our department. Paraffin sections of laryngeal SCC were immunohistochemically stained for p53, PCNA, and c-erbB-2. RESULTS: Overall, p53 overexpression was found in 16 patients. There was no relation between p53 immunohistochemical staining and tumor region. PCNA immunostaining was significantly stronger in supraglottic tumors compared with glottic tumors. Immunostaining of c-erbB-2 was not different in either location. There was no relation between the T stage of the tumor and p53 and c-erbB-2 immunostaining. However, there was a statistically significant positive correlation between the PCNA staining and T stage (stronger staining was present in T3 and T4 stages than in T1 and T2 stages). CONCLUSIONS: We could not find a statistically significant correlation between p53, PCNA, and c-erbB-2 and lymph node status, histologic differentiation, and survival rate. We demonstrated only a statistically significant positive correlation between PCNA staining and T stage. These data suggest that overexpression of p53, PCNA, and c-erbB-2 is not prognostic in laryngeal SCC.

Watermelon colon: is there an association with alcohol?

BACKGROUND: Watermelon colon, or rectal vascular ectasia of the colon, is a very rare vascular lesion. CASE REPORT: A 56-year-old male heavy drinker was admitted to hospital with hematochezia. Colonoscopy revealed linear, watermelon-like vascular stripes throughout the entire colon. Rectal biopsies confirmed the vascular nature of these lesions, showing dilated and trombosed capillaries in the lamina propria. He had neither cirrhosis nor portal hypertension. The watermelon-like lesions regressed spontaneously following the cessation of alcohol intake. CONCLUSIONS: This observation suggests that this condition can be triggered by alcohol.

Superficial basal cell carcinoma of the scalp mimicking seborrhoeic dermatitis.

Superficial basal cell carcinomas (BCC) comprise 9% to 11% of BCC, and are commonly found on the trunk or limbs. We report a case of a superficial BCC on the scalp that was misdiagnosed and treated as seborrhoeic dermatitis. Any erythematous plaque-type lesion of long duration must have superficial BCC considered in the differential diagnosis.