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PURPOSE: To report a case of tumoral calcinosis and to emphasize the importance of its correct and timely diagnosis. MATERIAL/METHODS: A 65-year-old former weaverworker female patient with a disease-free medical history underwent surgical removal of a subcutaneous painless mass of her left arm with a clinical diagnosis of a sebaceous cyst. The surgical specimen was fixed in formalin, the samples were embedded in paraffin blocks and histologic sections were taken and stain with hematoxylin- eosin. RESULTS: 1. Macroscopic findings: we received an irregular segment of skin and subcutaneous tissue d. 2.7 x 2.5 x 1.2 cm and multinodular chalky masses -the largest 0.4 cm in greatest dimension- were revealed in the dermis on sections. 2. Microscopic findings: Histopathologic examination revealed several calcified masses which did not contain necrotic tissue, with chronic and giant cell foreign body reaction and accompanying surrounding fibrosis forming partial encapsulation. These histopathologic data suggested the diagnosis of tumoral calcinosis. CONCLUSION: The identification of tumoral calcinosis in a biopsy specimen is of paramount importance as it may be correlated, apart from trauma, with various disorders such as hyperparathyroidism, sarcoidosis, scleroderma, hypermetabolic states and renal failure. In addition, the full knowledge of the preoperative patients„ medical history is necessary, otherwise undue alarm can be raised. [ABSTRACT FROM AUTHOR]

PURPOSE: Pseudomyxoma peritonei is a rare, chronic, relapsing, diagnostically challenging and poorly understood disease characterized by disseminated mucinous ascites and peritoneal implants. It is most commonly caused by an appendiceal primary cancer. We describe a case to emphasize the value of the cytologic evaluation of peritoneal fluid as a basic diagnostic test. MATERĠALS & METHODS: A 45-year-old male patient admitted to our hospital with abdominal and pelvic pain, bloating and digestive disorders. Two years earlier he had undergone surgery for an appendiceal tumor which histologically proved to be a low grade mucinous cystadenocarcinoma, so afterwards he received chemotherapy. A peritoneal washing was performed and the fluid was sent for cytologic evaluation. Smeras were prepared using the conventional and the liquid based methods abde were stain with Diff-Quick and Papanicolaou stains. RESULTS: The microscopic examination of the smears revealed the presence of extracellular mucin pools and relatively small rounded three-dimensioned clusters or irregular nuclear membranes, irregular chromatin distribution, variably sized nucleoli and occasionally mucinproducing features. Based on the above the diagnosis of pseudomyxoma peritonei was set. CONCLUSĠON: The cytomorphologic features and the patients‟ history are crucial factors for establishing a secure diagnosis of pseudomyxoma peritonei in peritoneal fluid which can lead to an accurate treatment. [ABSTRACT FROM AUTHOR]

Adenomyoepithelioma (AME) is an uncommon breast tumor distinguished by the presence of both epithelial and myoepithelial cell proliferation. It often presents clinically as a well-circumscribed, non-painful mass, although it can also be asymptomatic and discovered incidentally during imaging. This case report describes a 32-year-old woman with a tumor that progressively increased in size. It was initially assessed as a fibroadenoma based on ultrasonography and MRI, as the patient declined to undergo a core needle biopsy. The tumor poses significant diagnostic challenges due to its diverse imaging characteristics, necessitating a core needle biopsy for initial identification. There is also considerable variability within different regions of the same tumor, and surgical removal is typically recommended for most cases of AME. Most AMEs are benign, but they have the potential for local recurrence after surgical excision and, in rare cases, can become malignant. Accurate diagnosis and appropriate management can be achieved through clinical suspicion during examination, combined with the use of radiological techniques and histopathological analysis., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Rellias et al.)

Purpose of Review: Chronic granulomatous disease (CGD) is a primary immunodeficiency, with a defect of phagocytes in killing specific pathogens. CGD is characterized by severe recurrent bacterial and fungal infections and dysregulated inflammatory response. Since its first description as fatal disease about 60 years ago, a significant improvement in outcome has been achieved in the last 20 years. The purpose of this review is to framework recent advances in CGD immunopathogenesis, management of disease manifestation and cure of CGD patients., Recent Findings: For years, CGD is a known cause of life-threatening infections and excessive inflammation. The cause and the management of inflammatory reactions, however, have not been clarified, and the range of clinical presentation is growing with corresponding novel therapeutic interventions. Recent work focuses on the best outcome of hematopoietic stem cell transplantation (HSCT) and gene therapy for the cure of CGD patients, more specifically, those with X-linked and p47 mutations., Summary: The genetics and phenotype of CGD is well characterized; however, the underlying mechanisms, the treatment of its inflammatory manifestations and the cure of CGD is under further investigation.

Expression of thioredoxin-1 (TXN) and CXCL9 is not restricted to THRLBCL macrophages, but may be observed in histiocytes and neoplastic (HRS) cells of EBV + mixed cellularity (MC) classical Hodgkin lymphoma (cHL) and nodular lymphocyte predominant HL. We aimed to validate and extend the above observations in 174 cHL patients evaluating the immunohistochemical expression of TXN, CXCL9 and IFN-γ. HRS-cell CXCL9 expression was higher in latent membrane protein-1 (LMP1)+, MC and Stage IV. TXN and CXCL9 expression by cHL histiocytes was more frequent in LMP1+, MC and older patients (only for CXCL9). TXN expression by HRS cells (≥80%) was independently associated with better failure-free survival. In conclusion, markers of TCHRLBCL histiocytes (TXN, CXCL9), as well as IFN-γ are also expressed by histiocyte subsets and neoplastic cells of cHL. The expression of some of them is more prominent in EBV + MC, but not restricted to this subtype. The prognostic implication of TXN needs further evaluation.

Background: Celiac disease is a complex chronic immune-mediated disorder of the small intestine. Today, the pathobiology of the disease is unclear, perplexing differential diagnosis, patient stratification, and decision-making in the clinic., Methods: Herein, we adopted a next-generation sequencing approach in a celiac disease trio of Greek descent to identify all genomic variants with the potential of celiac disease predisposition., Results: Analysis revealed six genomic variants of prime interest: SLC9A4 c.1919G>A, KIAA1109 c.2933T>C and c.4268&#95;4269delCCinsTA, HoxB6 c.668C>A, HoxD12 c.418G>A, and NCK2 c.745&#95;746delAAinsG, from which NCK2 c.745&#95;746delAAinsG is novel. Data validation in pediatric celiac disease patients of Greek (n = 109) and Serbian (n = 73) descent and their healthy counterparts (n = 111 and n = 32, respectively) indicated that HoxD12 c.418G>A is more prevalent in celiac disease patients in the Serbian population (P < 0.01), while NCK2 c.745&#95;746delAAinsG is less prevalent in celiac disease patients rather than healthy individuals of Greek descent (P = 0.03). SLC9A4 c.1919G>A and KIAA1109 c.2933T>C and c.4268&#95;4269delCCinsTA were more abundant in patients; nevertheless, they failed to show statistical significance., Conclusions: The next-generation sequencing-based family genomics approach described herein may serve as a paradigm towards the identification of novel functional variants with the aim of understanding complex disease pathobiology.

Primary Immunodeficiencies (PID) represent a group of heterogeneous immune diseases with important biological significance. We reviewed the records of children diagnosed with PID in the Referral Center for PID in our country in order to describe the epidemiological, clinical and laboratory characteristics of immunodeficient patients. During a 30-year period, 147 patients (101 males, 68.7 %), with a mean age of 6.5 years at the time of diagnosis, were diagnosed with PID. The most prevalent diagnoses of PID were: "Combined Immunodeficiency" in 46 (31.3 %) patients, "Well-defined immunodeficiency syndrome" in 35 (23.1 %) patients, "Predominantly antibody deficiency" in 30 (20.4 %) patients and "Congenital defect of phagocyte function or both" in 28 (19 %) patients. There was a higher prevalence of males with "Combined immunodeficiency" (p < 0.033) and "Predominantly antibody deficiency" (p < 0.02) compared to females. The median age of children at the onset of symptoms and at the time of diagnosis was 0.5y (IQR: 0.1-2.5) and 2y (IQR: 0.6-7.2), respectively. The median diagnostic delay was 0.9y (IQR: 0.2-4.8). This period was shorter for patients with "Combined immunodeficiency" [median 0.3y (IQR: 0.1-1)], and longer for those with "Predominantly antibody deficiency" [median 3.2y (IQR: 0.2-5.9) or "Disease of immune dysregulation" [median 3.2y (IQR: 0.1-6.6)]. Comparing the rates in our population with those of the European Registry (ESID), the rates of "Combined immunodeficiencies", "Well-defined syndromes" and "Congenital birth defects and/or function of phagocytes" were significantly higher in this study (p <0,001). PID registry analysis improves knowledge in the field of Immunology and enhances awareness, early detection, diagnosis, and management of this rare but significant group of diseases.

Chronic Granulomatous Disease (CGD) is an uncommon primary immunodeficiency caused by the absence or dysfunction of one of NADPH oxidase subunits, with heterogeneous genetic aetiologies. The aim of this study was the CGD patient registry in Greece, the identification of the responsible genotype and the potential correlation with the patient's clinical phenotype. Medical charts of 24 CGD patients, investigated by NBT test or DHR for NADPH oxidase activity, Western blot analysis for NADPH oxidase component expression and DNA sequencing (pyro- and cycle sequencing) for mutation analysis, were reviewed. All patients, but one, were classified into the different types of CGD. Sixteen patients from 14 unrelated families had X-linked CGD (66.7 %), four had mutations in the NCF1 gene (19 %), and three, from two unrelated families, had mutations in NCF2 (9.5 %) [Corrected]. Fifteen mutations were detected in the CYBB gene, including nonsense (53.8 %), splice site (30.8 %) and missense mutations (7.7 %), and deletions (7.7 %). Two novel mutations were identified; one in CYBB and one in NCF1. Carrier detection for X-CGD revealed that the de novo mutation rate was about 7 %. Prenatal diagnosis identified one affected male in three male fetuses tested. In both the X-linked and the autosomal recessive (AR-CGD) group, the gastrointestinal and respiratory manifestations were more common, followed by lympadenopathy in X-CGD and skin infections in the AR-CGD group. The patients with a mutation in CYBB had a wider variability of clinical manifestations and earlier diagnosis (4.6 years) compared to the AR-CGD group (12.9 years). The incidence of CGD in Greece is estimated at 0.90 (95 % CI 0.89-0.91) per 100,000 live births for the last decade.

Background: Celiac disease (CD) has been associated with HLA class II heterodimers. This study aimed at determining the HLA genotypic and allelic distribution in Greek children with CD as compared with the general population., Methods: A total of 118 children with CD and 120 healthy individuals serving as controls were included in the study., Results: Higher frequencies for HLA-DQB1*02:01 (40.25 vs. 9.58%, P < 0.001) and DQB1*02:02 (20.34 vs. 5.42%, P < 0.001) were observed in patients with CD, whereas HLA-DQB1*03:01 (16.53 vs. 30.42%, P < 0.001), DQB1*05:01 (0.85 vs. 10%, P < 0.001), and DQB1*05:02 (5.51 vs. 17.92%, P < 0.001) were significantly lower, as compared with the controls. DQA1*02:01 (patients with CD vs. controls: 20.76 vs. 6.67%, P < 0.001) and DQA1*05:01 (40.25 vs. 9.58%, P < 0.001) were significantly more frequent in patients. The frequencies of HLA-DQA1* 01:01, *01:02, *01:04, and *05:05 were significantly lower in patients (P < 0.001). The haplotype mainly associated with CD was DRB1*03-DQB1*02:01-DQA1*05:01; patients with CD vs. controls: 39.83 vs. 9.58%, P < 0.001. In total, 84.75% of patients carried DQ2 (vs. 21.67% in controls, P < 0.001), whereas 11.02% were DQ8 positive/DQ2 negative., Conclusion: This study confirms the existing data and provides additional evidence supporting a strong genetic predisposition for CD associated with the class II alleles DQB1*02 and DQA1*05 encoding the serological specificity DQ2.

Various polymorphisms in cytokine genes have recently been investigated as candidate risk factors in allogeneic hematopoetic stem cell transplantation (allo-HSCT). We retrospectively analyzed specific polymorphisms in genes for interleukin (IL)-10, IL-6, tumor-necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) in a pediatric cohort of 57 histocompatibility leucocyte antigen (HLA)-identical sibling myeloablative transplants. Both recipient and donor genotypes were tested for association with graft-versus-host disease (GVHD) by statistical methods including Cox regression analysis. We found a significant association between the IL-10 promoter haplotype polymorphisms at positions -1082, -819 and -592 with the occurrence of severe (grades III-IV) acute GVHD (aGVHD). Recipients with the haplotype GCC had a statistically significant decreased risk of severe aGVHD (hazard risk (HR)=0.20, 95% confidence interval (CI): 0.06-0.67) in comparison with patients with other IL-10 haplotypes (P=0.008). Transplant-related mortality at 1 year was significantly lower in recipients with this haplotype (HR=0.17, 95% CI: 0.012-0.320) versus other IL-10 haplotypes (P=0.03), whereas overall survival was not influenced by IL-10 haplotype polymorphisms. In multivariate analysis, the presence of the IL-10 GCC haplotype was found as the only variable associated with a statistically significant decreased hazard of severe aGVHD development (P=0.02, HR=0.21, 95% CI: 0.05-0.78). These results suggest that pediatric patients possessing the IL-10 GCC haplotype may be protected from the occurrence of severe aGVHD in the setting of matched sibling HSCT.

Rigid telescopic strobo-video-laryngoscopy (RTS) is a primary clinical assessment methodology in the office evaluation of benign glottic lesions. However, diagnostic observations can be made only at the time of suspension microlaryngoscopy (SML). The records of 100 consecutive patients undergoing microlaryngoscopy for benign glottic lesions were retrospectively reviewed. Nine of 100 patients were found to have additional glottic lesions during SML. Sixteen additional lesions were noted in these nine patients. Fifteen of 16 lesions were sulci and/or mucosal bridges. Forty-five percent (4/9) of the patients with additional lesions underwent a management change intraoperatively. Three patients underwent additional surgical dissection, and one underwent less dissection than was planned. The discrepancy in diagnosis between rigid telescopic strobo-video-laryngoscopy and suspension microlaryngoscopy highlights certain key points: (1) During office endoscopy, tangential views of the medial surface of the glottis limit the diagnostic sensitivity. (2) Sulci and mucosal bridges are most subject to this limitation. (3) Informed consent should address the potential need for a change in intraoperative management. It is advisable to discuss the possibility for dissection in both vocal folds, even if a unilateral lesion is observed in the office. (4) Microlaryngoscopy is the final diagnostic step in the evaluation of glottic pathology. Meticulous inspection and palpation of the glottis are recommended during SML.

Disruption of the normal viscoelastic properties of the superficial lamina propria (SLP) results in aberrant vocal fold vibration and mucosal wave propagation. Therefore, an investigation was performed to determine whether stroboscopy is a reliable method for 1) differentiating invasive glottic carcinoma from intraepithelial atypia or 2) determining the depth of cancer invasion. An analysis was done on the preoperative vocal fold vibration characteristics of 62 keratotic (intraepithelial, 45; cancer, 17) lesions that were subsequently resected by means of microlaryngoscopy. Histopathology and intraoperative mapping were used to specify the depth of invasion. A panel of 4 blinded judges was used to assess the amplitude of vocal fold vibration and the magnitude of mucosal wave activity in the region of the lesion from videostroboscopic recordings. The final comparative data set comprised only those ratings that achieved at least 75% interjudge agreement. Of the 28 intraepithelial lesions that could be reliably evaluated for amplitude of vocal fold vibration, only 2 were normal, with the amplitude reduced in 24 and absent in 2. Of the 30 intraepithelial lesions in which mucosal wave activity could be reliably assessed, only 2 were normal, with the wave reduced in 24 and absent in 4. Furthermore, amplitude of vocal fold vibration and magnitude of mucosal wave propagation were absent in 2 of 4 carcinomas in which the depth of microinvasion did not reach the vocal ligament. According to the findings herein, reduced amplitude of vocal fold vibration and/or mucosal wave propagation associated with keratosis did not reliably predict the presence of cancer or the depth of cancer invasion into the laminae propriae. However, the presence of a flexible mucosal wave probably indicates that there is not extensive vocal ligament invasion. Reductions in the amplitude of vocal fold vibration and in mucosal wave magnitude were usually noted in intraepithelial atypia, despite the fact that there was no invasion into the SLP. The reduced epithelial pliability could be due to bulky keratosis and/or alteration of the SLP occurring as a result of inflammation or fibrovascular scarring.