Ioannis G. Panayiotides

Infections caused by filamentous fungi other than Aspergillus spp. or Mucorales are uncommon but often severe, particularly in immunocompromised individuals. We conducted a prospective, nationwide, multicenter study to investigate the epidemiology, clinical spectrum, antifungal susceptibility, treatment, and outcomes of invasive and severe localized rare mold infections in Greece from 2009 to 2025. We documented 118 cases, with no significant temporal trend. The most frequent underlying conditions were hematologic malignancy (27.1%), hematopoietic cell transplantation/graft-versus-host disease (11.9%), trauma or other skin conditions (13.6%), pulmonary disease or respiratory failure (5.9%), and ocular predisposing factors for keratitis (22.9%). Bloodstream and corneal infections predominated. Fusarium spp. accounted for 66.9% of cases, followed by Scedosporium apiospermum (9.3%). Six breakthrough infections occurred during mold-active prophylaxis or empirical treatment, all caused by Fusarium spp. Amphotericin B showed the greatest in vitro activity against Fusarium spp., whereas voriconazole was most active against non-Fusarium molds. Clinical outcomes did not consistently correspond with in vitro antifungal activity. Crude mortality among non-ocular infections was 44.4% and was significantly higher in patients with hematologic malignancy or hematopoietic cell transplantation than in other patients (65% vs. 28%; p = 0.018). The number of reported rare mold infections in Greece showed no increasing trend, but they were associated with substantial morbidity and high mortality, particularly among severely immunocompromised patients.

Invasive lobular carcinoma (ILC) is the most common special type of breast carcinoma, accounting for 5–15% of all breast carcinoma cases. Its metastatic pattern differs from that of invasive breast carcinoma of no special type, with ILC metastases to the peritoneum, gastrointestinal tract, and female genital tract being more frequent. This literature review focuses on ILC cases with metastasis to the female genital tract (FGT). Searches were conducted in medical databases including PubMed, Scopus, and Web of Science, using specific keywords. Inclusion criteria centered on studies presenting one or more cases of patients with ILC metastasis to the FGT and English language publications. Exclusion criteria included articles that did not present original research findings, studies with insufficient data, and publications in languages other than English. A thorough analysis of 154 results from PubMed, 56 from Scopus, and 173 from Web of Science after the application of inclusion and exclusion criteria resulted in the inclusion of 54 manuscripts describing 61 cases. The demographic, clinicopathological, and therapeutic aspects of ILC metastases to the FGT were reviewed and the differential diagnosis and prognosis for each anatomic location in the FGT were discussed separately. Our analysis of the data showed that the restricted mean survival time was 186 ± 30.7 months and that a negative ER on a secondary tumor was found to be linked to worse patient survival rates. Also of note is the fact that in 37.7% of cases there was involvement of multiple FGT anatomic locations and in 36% of cases there were metastases in organs or anatomic locations other than the FGT. To our knowledge, our study is the only one to describe the features of patients with secondary FGT involvement from ILC.

Invasive lobular carcinoma (ILC) is the most common special type of breast carcinoma, accounting for 5-15% of all breast carcinoma cases. It exhibits several unique features in morphology, clinical behavior, radiological features, molecular characteristics, and metastatic pattern. The latter differs from that of invasive breast carcinoma of no special type with ILC metastases to the peritoneum, gastrointestinal tract, and female genital tract being more frequent. We herewith review the demographic, clinicopathological, and therapeutic aspects of ILC metastases to the female genital tract and discuss separately the differential diagnosis and prognosis for each anatomic location of the female genital tract.

Background/Objectives: There are limited data regarding immunohistochemical profiling of immune cells in bone marrow trephine biopsies of patients with high-risk myelodysplastic syndromes (HR-MDS). Methods: We sought to objectively quantify, with the use of digital pathology, the density (cells/mm2) of the prominent adaptive immunity cell populations in sixty-four (64) bone marrow trephine biopsies of HR-MDS patients receiving 5-Azacytidine. We focused on CD3(+) T cells, CD8(+) cytotoxic T cells (Tc), helper T cells (Th), Foxp3(+) regulatory T cells (Tregs), CD20(+) B-cells and CD138(+) plasma cells and evaluated the presence and the number of lymphoid aggregates. A control group of twenty “non-MDS” patients was included in the study. Results: We identified a significant decrease in adaptive immune cell densities in the HR-MDS patients compared to the non-MDS controls. Increased T and Th cell densities correlated with the response to 5-Azacytidine (5-AZA) treatment. Higher T, Tc, Th and plasma cells densities and low B, Tregs and Tregs/T cells ratios correlated with increased overall survival. Reduced Tregs, Tregs/T cells, Tregs/Tc and plasma cells showed improved leukemia-free survival. A modified IPSS-R (IPSS-R-I), combining the initial IPSS-R with the immune populations’ parameters, improved overall survival and showed a double-fold increase in Cox calculated hazard ratios. Conclusions: Immunohistochemical bone marrow immune profiling represents a powerful and easily useable tool for investigating the possible role of bone marrow immune microenvironment in the pathogenesis and progression of MDS, but also its association with the response to 5-AZA treatment and clinical outcomes.

DICER1 syndrome (DICERs) represents a tumor predisposition genetic syndrome, inherited in an autosomal dominant manner. Germline loss-of-function variants of the DICER1 gene lead to impaired processing of microRNA, gene expression, and increased risk of tumorigenesis. Although pleuropulmonary blastoma (PPB) is the hallmark of the syndrome, multiple extrapulmonary malignant and non-malignant conditions have also been described, including multinodular goiter (MNG) and sex-cord stromal tumors. MNG is one of the most common components and is associated with an increased risk of thyroid carcinoma. Sertoli–Leydig cell tumor (SLCT) represents the most prevalent type of sex-cord stromal tumor associated with the syndrome, whereas juvenile granulosa cell tumor (JGCT) is considered to be a very rare phenotype. They both may present with abdominal pain due to mass effect and menstrual irregularities in case of hormone production. Although they exhibit low rates of mortality, recurrence rates highly depend on the grade of malignancy. Herein, we report a novel pathogenic DICER1 variant associated with MNG, bilateral ovarian SLCT, and JGCT in a young Greek patient. Clinicians should be aware of a potential germline DICER1 variant when evaluating MNG in young patients, especially if it coexists with other neoplasms.

Breast carcinoma is the most common cancer in women. Nineteen different subtypes of breast carcinomas are recognized in the current WHO classification of breast tumors. Except for these subtypes, there are a number of carcinomas with special morphologic and immunohistochemical features that are not included in the 5th WHO classification, while others are considered special morphologic patterns of invasive breast carcinoma of no special type. In this manuscript, we systematically review the literature on four different subtypes of invasive breast carcinoma, namely lymphoepithelioma-like breast carcinoma, breast carcinoma with osteoclast-like giant cells, signet-ring breast carcinoma, and metaplastic breast carcinoma with melanocytic differentiation. We describe their clinicopathological characteristics, focusing on the differential diagnosis, treatment, and prognosis.

Introduction: Endometriosis is a common benign condition affecting 10–15% of women of reproductive age. An unusual site of endometriosis is the canal of Nuck, which is a physiologically obliterated space in women spanning the area from the deep inguinal ring to the labia majora. Case presentation: A 37-year-old woman, with a past medical history of several in vitro fertilization attempts, presented with a right-sided painful inguinal mass. She was subsequently offered surgical exploration and excision of the lesion, which revealed the presence of endometrial glands and stroma. Discussion: Despite being a relatively common and benign pelvic condition, endometriosis can rarely manifest in the inguinal region, within the canal of Nuck. The treating physician should be cognizant of Nuck canal endometriosis, especially in young female patients presenting with an irreducible mass in the inguinal region and associated cyclic pain or infertility. Conclusion: When clinically and radiologically suspected, surgical excision is indicated to establish the diagnosis, provide symptomatic relief and guide further decision making.