Iranian Journal of Pathology最新文献

A rare condition, blastic plasmacytoid dendritic cell neoplasm, is classified as acute myeloid leukemia-related precursor neoplasms according to the World Health Organization's 2022 classification. Previously thought to originate from natural killer cells, T cells, or monocytes, it is now believed to arise from plasmacytoid dendritic cells. The cause of this condition is not well understood, but it is often associated with the deletion of tumor suppressor genes such as RB1, CDKN1B, CDKN2A, and TP53. The disease is aggressive and typically presents with initial cutaneous lesions that can progress to bone marrow involvement and leukemic dissemination. Flow cytometry/ immunohistochemistry can detect enhanced CD56, CD4, and CD123 expression. The differential diagnoses include myeloid sarcoma/acute myeloid leukemia, T-cell lymphoblastic leukemia/lymphoma, NK-cell lymphoma/leukemia, and certain mature T-cell lymphomas/leukemias. Although initial chemotherapy may elicit a patient response, relapse is common. Survival may be improved by stem cell transplantation. This case report details the medical history of a 64-year-old woman who presented with a skin mass that exhibited slow growth over 6 months. The mass was firm on palpation. Extensive testing, including a bone marrow (BM) smear and biopsy, revealed numerous abnormal or blastic cells. Furthermore, flow cytometric analysis of the BM confirmed the presence of plasmacytoid dendritic cell-neoplastic precursor cells exhibiting CD4+ and CD56+ characteristics.

Background & objective: Luminal B breast cancer (LBBC) is on the rise worldwide, with both incidence and mortality rates steadily increasing. Early detection proves difficult due to its aggressive characteristics, most notably its heightened proliferation rate and the complex interplay of molecular biomarkers, particularly in more advanced stages.

Methods: Data Sources: In the present study, we conducted an in-silico analysis of LBBC cell lines using the Gene Expression Omnibus (GEO) microarray dataset, which includes 30 LBBC and 11 normal samples. Analysis Tools: Differentially expressed genes (DEGs) were identified using RStudio. A series of analyses, including cancer data interrogation via pan-cancer analysis, eXpression2Kinases (X2K), and the Cancer Dependency Map (DepMAP), was carried out to elucidate the underlying signaling pathways, transcription factors (TFs), and kinases, as well as to perform stemformatics analysis. Protein-protein interaction (PPI) networks were reconstructed using STRING and Cytoscape, enabling the identification of co-expressed and hub genes through the cytoHubba plug-in.

Results: Of notes, FGF2, EGFR, ADIPOQ, LIPE, MET, IGF1, FGF1, EGF, FGF7, and PPARG were identified as the top 10 hub genes; RELA, PPARG, CTCF, EGR1, and NFE2L2 were detected as predominant TFs in LBBC; and CDK1, CDK2, MAPK3, CSNK2A1, and MAPK14 were identified as potential biomarkers through hub gene clustering. Further analysis indicated hsa-mir-221-3p and hsa-mir-29a-3p as key miRNAs targeting LBBC-related genes.

Conclusion: Collectively, our findings highlighted LBBC-associated genes, TFs, miRNAs, and pathways as prospective biomarkers, providing insights into LBBC diagnosis and therapeutic approaches.

Background & objective: Sinonasal melanoma is an aggressive malignancy with a poor prognosis, largely due to its propensity for local invasion and early metastasis. Diagnosis is often difficult, particularly in the absence of melanin pigmentation. Histopathological and immunohistochemical (IHC) evaluation is essential for confirmation. This report describes a diagnostically challenging case of amelanotic melanoma of the sinonasal region.

Case presentation: A 56-year-old woman presented with a 5-month history of epistaxis, facial pain, and visual impairment of the left eye. Clinical examination revealed a mass in the left nasal cavity, initially diagnosed as sinonasal carcinoma. Histopathology suggested a differential diagnosis of non-Hodgkin lymphoma (NHL) and poorly differentiated squamous cell carcinoma (SCC). Imaging demonstrated a sinonasal tumor involving the left extraconal orbital wall and paranasal sinuses. A biopsy initially raised suspicion for NHL; however, IHC staining was negative for CD45, CD20, and CD3. Similarly, negative P40 and cytokeratin excluded SCC. Strong immunoreactivity for S100, HMB45, and Melan-A established the diagnosis of amelanotic melanoma.

Conclusion: Amelanotic melanoma of the sinonasal tract poses a significant diagnostic challenge due to nonspecific clinical features and lack of pigmentation. This case highlights the indispensable role of IHC in achieving a definitive diagnosis.

Background & objective: Even with improvements of colorectal cancer (CRC) treatment strategies, this cancer still has an unfavorable outcome. The primary cause of CRC development and recurrence is chemoresistance. CD10 and Notch1 are among cancer stem cell regulators, and they have roles in cancer progression and chemoresistance. This research aims to evaluate the expression of Notch1 and CD10 in CRC and their relationship with different clinicopathological parameters using immunohistochemistry.

Methods: This retrospective study included 100 cases of colorectal carcinoma that were immunohistochemically stained using Notch1 and CD10 antibodies. Expression of Notch1 and CD10 was evaluated and compared with different clinicopathological parameters.

Results: Notch1 expression was detected in the tumor and stromal cells in 92% of the cases, while CD10 expression was seen in 31% of tumor cells 79% of stromal cells of the included cases. Their expressions in tumor cells were significantly associated with higher grade (P=0.029 and 0.001), deeper invasion (P=0.01 and 0.002), advanced stage (P=0.012 and 0.001), and distant metastasis (P=0.001 and 0.02). Notch1 expression was positively correlated with CD10 expression (P=0.018). Both Notch1 expression and high CD10 expression in the stromal cells were associated with short overall survival (P=0.003 and 0.01).

Conclusion: CD10 and Notch1 may have roles in colorectal carcinoma progression via induction of tumor invasion, metastasis and impairment of tumor response to therapy. CD10 and Notch1 could be used as biomarkers for aggressive CRC and may be considered for future target therapy.

Background & objective: Mucormycosis has emerged as a severe complication in COVID-19 patients, particularly among those with uncontrolled diabetes and those receiving corticosteroid therapy. The infection's tendency to spread from the sinuses to the orbit and central nervous system (CNS) significantly increases morbidity and mortality. This study aimed to identify clinical risk factors and outcomes associated with disease severity and mortality in COVID-19-associated mucormycosis (CAM), with a focus on disease progression to orbital and CNS involvement.

Methods: A total of 180 confirmed CAM patients were enrolled and classified into three groups based on disease extent: sinus-only, sinus with orbital involvement, and sinus with both orbital and CNS involvement. Data were collected on demographics, clinical history, laboratory findings, imaging results, treatment modalities, and outcomes.

Results: Of the 180 patients, 63.3% had sinus-only involvement, 23.9% had sinus and orbital involvement, and 12.8% had sinus, orbital, and CNS involvement. Uncontrolled diabetes was observed in 38% of patients and was more prevalent in those with extensive disease. Corticosteroid use was significantly associated with disease severity (p = 0.002). Invasive procedures, such as orbital exenteration, were significantly linked to CNS progression (p < 0.05). The overall mortality rate was 31% (55 of 180 patients).

Conclusion: Uncontrolled diabetes and corticosteroid therapy are major risk factors for severe CAM. Extension of mucormycosis beyond the sinuses, particularly to the orbit and CNS, is associated with poor clinical outcomes and often requires aggressive surgical management. Early diagnosis and prompt intervention are essential to improve survival in these patients.

Background & objective: Although the concordance between immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) is generally high for HER2 scores of 3+ and 1+, discrepancies remain in cases scored as IHC 2+. This study aimed to evaluate HER2/neu gene amplification using FISH in breast cancer patients with IHC 2+ and to examine associated clinicopathological characteristics.

Methods: This retrospective study included tissue samples from 369 women diagnosed with invasive ductal carcinoma of the breast and an equivocal HER2 IHC score (2+). These samples were further assessed for HER2 gene amplification using FISH. Demographic and clinicopathological data were collected and analyzed.

Results: The mean age of patients was 51.6 ± 2.6 years. FISH analysis revealed no HER2 amplification in 72.6% of IHC 2+ cases, while 27.4% demonstrated amplification. HER2 amplification was significantly associated with younger age, higher histological grade, lymph node involvement, larger tumor size, and reduced survival rate. No significant association was observed between HER2 amplification and margin involvement.

Conclusion: HER2 amplification is a significant predictor of aggressive tumor behavior and may necessitate targeted therapy. In cases with IHC 2+, both FISH results and relevant clinicopathological features should be considered prior to initiating trastuzumab treatment.

Background & objective: CD58 and ADAM10 have been implicated in leukemia progression and chemoresistance; however, their specific roles in acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL), particularly under chemotherapeutic pressure, remain insufficiently characterized. This study aimed to assess the expression of CD58, an immune adhesion molecule, and ADAM10, a metalloproteinase, in ALL and CLL patients undergoing chemotherapy, and to explore their potential involvement in immune evasion, niche-mediated survival, and chemoresistance mechanisms.

Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from 50 patients with ALL, 50 with CLL, and 30 healthy controls. Expression levels of CD58 and ADAM10 were analyzed by quantitative reverse transcription PCR (qRT-PCR) and flow cytometry. Chemotherapy regimens included vincristine (VCR), methotrexate (MTX), and doxorubicin (DOXO).

Results: ADAM10 mRNA expression was significantly upregulated in ALL patients treated with VCR+MTX (p<0.0001) and DOXO (p=0.001), with corresponding protein overexpression observed in both ALL (p<0.0001) and untreated CLL patients (p<0.0001). A significant difference in ADAM10 levels was noted between ALL and CLL cohorts (p=0.001). CD58 mRNA and protein expression were markedly increased in ALL patients receiving VCR+MTX (p<0.0001), whereas untreated CLL patients exhibited no significant alterations.

Conclusion: CD58 and ADAM10 are differentially regulated in ALL under chemotherapy, supporting their roles in immune evasion and microenvironmental survival. The constitutive overexpression of ADAM10 in CLL suggests its involvement in chronic leukemic pathogenesis. These findings highlight CD58 and ADAM10 as potential therapeutic targets for overcoming chemoresistance in lymphoid malignancies.

Congenital pulmonary airway malformation (CPAM) is a structural anomaly that occurs during development of the lower respiratory tract. We describe a 4-day-old male infant with this uncommon congenital anomaly. He presented with respiratory distress and low oxygen saturation. A chest radiograph showed infiltration in the right lower lobe, and a chest computed tomography (CT) revealed alveolar opacity with an air bronchogram pattern in the right lung along with mediastinal shift. The right lower lobe was surgically resected. Pathological examination showed an 8-cm, predominantly solid cut surface with a rare tiny cyst, consistent with a congenital cystic adenomatoid malformation (type 3). Congenital pulmonary airway malformations are the most common congenital parenchymal lung anomalies. Although their development is debated, it is believed to result from a halt in fetal bronchial tree growth between the sixth and seventh weeks of fetal life. Flaws in thyroid transcription factor 1 have also been proposed. With the widespread use of high-quality ultrasonography in modern obstetrics, it is now less likely for congenital pulmonary airway anomalies to remain undetected until adulthood. Early surgical excision is generally recommended. However, in asymptomatic infants, management remains controversial because either operative or non-operative approaches may be used later in life, particularly in light of complications such as the potential for mucinous adenocarcinoma with a lepidic-predominant pattern. Patients with this condition in neonatal intensive care units should be managed by a multidisciplinary team that includes pediatric surgeons, neonatologists, and radiologists.

Background & objective: Nonalcoholic fatty liver disease, recently recognized as metabolic dysfunction-associated steatotic liver disease (MASLD), is a key factor in the development of chronic liver disease and the progression of liver fibrosis. It plays a significant role in increasing the risk of cirrhosis and hepatocellular carcinoma. Given the rapid developments in this field, keeping information up-to-date is essential to prevent misconceptions and ineffective decision-making. This study employs a scientometric approach to review scientific literature and analyze recent findings, offering a comprehensive overview of the current state of research in this field.

Methods: In this approach, we explored data related to publication metrics, public perceptions, scientific conference, mobile apps, AI tools, and new medications. This was done using a set of keywords, including "Non-alcoholic fatty liver disease," "Metabolic dysfunction-associated steatotic liver disease," "Mobile application," and "Artificial intelligence."

Results and conclusion: This research highlights significant scientific advances in the field of MASLD, including major scientific meetings, highly cited publications, and the latest FDA-approved therapies. In addition, it examines emerging digital tools and public search frameworks, providing a structured picture of recent developments. These findings provide a comprehensive view of the dynamic MASLD research landscape and emphasize the roles of AI, mobile apps, and emerging therapies in its management.