PATHOLOGICA最新文献

The AFF2 gene encodes a protein involved in transcriptional regulation and chromatin remodeling. While primarily associated with Fragile X syndrome, AFF2 fusions have recently been identified in certain malignancies, mostly sinonasal squamous cell carcinoma. Recently it has been implicated in an intra-abdominal sarcoma linked to endometriosis. We present the case of a 71-year-old woman with a 19 cm ovarian mass arising in cystic endometriosis. Histological examination revealed high-grade undifferentiated sarcoma with spindle to epithelioid morphology, high nuclear atypia, a high mitotic index, and extensive necrosis. Immunohistochemistry demonstrated positivity for Vimentin, ER, PR, CD10, focal WT1, Desmin, and NTRK, with aberrant p53 expression in 75% of tumor cells. RNA sequencing identified a novel ZDHHC9::AFF2 fusion. The patient underwent chemotherapy with epirubicin and ifosfamide but experienced recurrence with lymph node and peritoneal involvement and succumbed to the disease after 9 months.

In conclusion, this case expands the morphological spectrum of AFF2-related sarcomas, providing further evidence of their pathological heterogeneity. Moreover, it identifies a novel fusion, which may have implications for tumor classification and diagnostic refinement. The morphological findings also suggest a possible association with poor clinical outcomes.

Solitary fibrous tumor (SFT) is a rare spindle cell neoplasm showing fibroblastic differentiation, initially observed in the pleura, but now currently recognized to develop in any extrapleuric location ^1,2. In the female genital tract, SFTs are extremely rare and have a predilection for the vulva, vagina and cervix ^2,3. There are very few cases of ovarian SFTs having been reported in the literature. Malignant SFTs of the ovary are exceedingly rare neoplasms characterized by their mesenchymal origin and distinctive histopathological features. First identified as a separate entity in soft tissues, SFTs of the ovary represent a diagnostic and therapeutic challenge due to their rarity and overlapping characteristics with other ovarian neoplasms. These tumors are generally considered benign, but their malignant variants can exhibit aggressive behavior, including metastasis and recurrence. The pathogenesis of SFTs is associated with molecular abnormalities, particularly NAB2-STAT6 gene fusions ⁴, which play a crucial role in diagnosis and may have prognostic implications. Our case of ovarian malignant SFT showed an unusual pattern of dedifferentiation. The conventional SFT component displays a pattern less architecture, uniform fibroblastic morphology, prominent branching vessels, and is diffusely positive for CD34 and STAT6. However, there is an abrupt transition to a pleomorphic, high mitotic rate component with fascicular spindle cell morphology resembling a smooth muscle neoplasm. This dedifferentiated area is positive for SMA and desmin but negative for CD34 and STAT6 and includes focal ossification. Stains for MDM2, CDK4, and caldesmon are negative. The case is notable for its atypical progression, as most dedifferentiated SFTs transition directly from a benign-appearing SFT to a high-grade component without signs of malignancy in the conventional SFT region.

Objective: Traditional pathological examination of lymph nodes is labor-intensive and has shown variability in diagnostic accuracy. Recent advancements in artificial intelligence (AI) provide promising opportunities to enhance and standardize pathological workflows. AI-based image analysis models, particularly those utilizing deep learning algorithms, have demonstrated potential in automating and improving diagnostic accuracy in histopathology. This study aimed to evaluate the performance of a novel AI model known as ChatGPT-4 in detecting metastatic involvement in sentinel lymph nodes (SLNs) from breast cancer cases.

Methods: We utilized digital slides from frozen sections, which are commonly employed intraoperatively, to assess the model's diagnostic accuracy. A total of 90 SLNs were retrospectively collected and analyzed using ChatGPT-4. The generated diagnoses were evaluated by two senior pathologists.

Results: The AI model achieved an overall accuracy of 92.2%, with a sensitivity of 100% and specificity of 80.6%. The study highlights the practical applicability of AI in diagnosing SLN metastasis, emphasizing the importance of frozen sections in real-world scenarios.

Conclusions: These findings suggest that integrating AI models like ChatGPT-4 into pathological workflows could enhance diagnostic accuracy and efficiency in breast cancer treatment.

Primary thymic mucoepidermoid carcinoma (TMEC) is extremely rare and only a few cases have been reported in the literature. We describe the case of a TMEC in elderly man, with atypical morphological features that could lead potential diagnostic pitfall. Herein, we suggest a practical approach that may help guide pathologists in their differential diagnosis to distinguish TMEC from other thymic mimics.

Background: Most pancreatic ductal adenocarcinoma (PDAC) are diagnosed with fine needle aspiration biopsies (FNAB). Some benign mimickers exist, and the differential diagnosis can be challenging. Immunohistochemistry (IHC) is a useful diagnostic tool, and some biomarkers have been studied in this clinical setting. Homozygous deletion (HD) of CDKN2A is observed in about 40% of PDAC, and methylthioadenosine phosphorylase (MTAP) IHC has been identified as a reliable surrogate marker for this alteration. The aim of our study is to evaluate the value of MTAP IHC status in the diagnosis of PDAC.

Materials and methods: We collected 27 EUS-FNAB of pancreatic masses. MTAP and S100P IHC were performed. The IHC status of MTAP has been correlated with CDKN2A molecular status studied by fluorescence in-situ hybridization (FISH) and next-generation sequencing (NGS).

Results: Approximately 25% of FNAB diagnosed as PDAC showed complete loss of MTAP expression. Our results demonstrated a very high positive predictive value (100%), with a modest sensitivity (31.5%) but a high specificity (100%) for the diagnosis of PDAC. Regarding S100P, 71% of PDAC cases tested positive, whereas the only case diagnosed as benign was negative. The concordance between CDKN2A molecular status by FISH and MTAP expression by immunohistochemistry did not prove to be optimal. Interestingly, some FISH wild-type samples showed HD in NGS.

Discussion: An immunohistochemical immunohistochemical panel including MTAP and S100P improves diagnostic accuracy in PDAC diagnosis, showing a better sensitivity (75%) and the same specificity compared to single markers. FISH showed an incomplete sensitivity in identifying all cases with HD of CDKN2A, with two cases MTAP negative by IHC and identified as deleted only by molecular study.

SMARCA4-deficient tumors of the thoracic cavity represent a newly emerging group of aggressive neoplasms driven by inactivation of the SMARCA4 gene, a key member of the SWI/SNF chromatin remodeling complex. These tumors are broadly classified into thoracic SMARCA4-deficient undifferentiated tumors (SMARCA4-UT) and SMARCA4-deficient non-small cell lung carcinomas (SMARCA4-dNSCLC). Despite some overlap in genomic alterations, especially smoking-related mutations like TP53, KRAS, and KEAP1, these entities differ in histomorphology, immunoprofile, and biological behavior. SMARCA4-UTs are undifferentiated, often rhabdoid in appearance, with loss of epithelial markers and gain of stem cell markers such as SOX2 and SALL4, while SMARCA4-dNSCLCs retain some epithelial differentiation. Radiologically, these tumors often present as large central thoracic masses with high metabolic activity and early metastases. Both tumor types show poor prognosis, with limited response to conventional therapies. Immunotherapy, particularly immune checkpoint inhibitors, shows promise even in PD-L1-negative cases, and emerging epigenetic and molecular targeted therapies are under investigation. It is crucial to distinguish SMARCA4-UT and SMARCA4-dNSCLC by appropriate use of histopathology, immunohistochemistry, and molecular studies, considering the prognosis and treatment response. Our review focuses on the advancement of understanding the clinicopathological spectrum of both entities, their genetic landscape, and current treatment options.

Aims: Molecular analysis of FGFR2 aberrant transcripts became crucial for clinical stratification of intrahepatic cholangiocarcinoma (iCCA) patients. Several strategies, including fluorescent in situ hybridization (FISH) and next generation sequencing (NGS), are commonly used to investigate FGFR aberrations. Here, we evaluated the technical performance of clinically implemented diagnostic strategies in 8 referral Italian institutions on artificial reference formalin-fixed paraffin-embedded (FFPE) samples.

Methods: Each participating institution was requested to apply its own diagnostic testing strategy on 8 sections obtained from artificial reference specimens built to harbor FGFR3(17)-TACC3(11) rearrangement and unbalanced FGFR2. A second-round slide set hosting FGFR2(17)-BICC1(3) aberrant transcript was shared to detect clinically relevant FGFR2 fusion. Artificial reference sample was previously validated by the University of Naples Federico II before arranging the shipment. Technical procedures (e.g. extraction methods, testing platforms and assays) were recorded.

Results: Overall, cell resuspension yielded higher amounts of DNA and RNA (SNU16 61.5 ng/µl, 38100.0 pg/µl; RT112 118.0/µl, 2140.0 pg/µl, respectively) in comparison with SNU16+ RT112 mixing cell block (0.7 ng/µl DNA and 412.0 pg/µl RNA). Moreover, FFPE samples showed a higher fragmentation index (DIN 1.2 and RIN not calculated) compared with cell line resuspension (DIN 2.2 and 9.5 for SNU16 and RT112; RIN 3.9 and 6.8 for SNU16 and RT112). All participating institutions identified FGFR2(17)-BICC1(3) and FGFR3(17)-TACC3(11) aberrant transcripts. Moreover, ID#2, ID#4, ID#7 institutions also detected FGFR2(3)-CD44(1) rearrangement on RNA, whereas institutions ID#1, ID#2, ID#3, ID#5, ID#6, ID#8 identified FGFR2 CNVs on DNA.

Conclusions: NGS represents the most suitable approach in molecular profiling of FGFR aberrant transcripts. Rings trial based on artificial reference samples play a pivotal role in optimizing routine diagnostic procedures filling the gap in clinical stratification of iCCA patients.

Methylation of CpG islands plays a crucial role in the regulation of gene expression. The study of DNA methylation profiles offers deep insights into key oncogenic processes and facilitates the differentiation of tumor entities at the epigenetic level. Methylation profiling was performed on 8 CNS tumors (6 children, 1 adolescent, 1 young adult) with inconclusive diagnoses, available frozen tissue, and surgeries dating back over 5 years. Our goal was to correlate the resulting methylation classes with the clinical-radiological data and to evaluate the diagnostic and prognostic power of this analysis. The resulting molecularly defined diagnoses were: pilocytic astrocytoma (3 cases), pilocytic astrocytoma subclass FGFR1 altered (1 case), ganglioglioma (2 cases), diffuse leptomeningeal glioneuronal tumor subtype 1 (1 case), and diffuse midline glioma H3.3K27-altered, subtype H3K27 mutant or EZHIP-expressing (1 case). Clinico-pathological features of each tumor in our series are discussed. The clinical behavior was consistent with the molecular diagnosis in all cases but one that was lost to follow-up. In our series, the initial diagnostic failure in 3 of the 8 cases was due to the fact that the pathological entities-diffuse midline glioma, H3 K27-altered, pilocytic astrocytoma with FGFR1 alteration and diffuse leptomeningeal glioneuronal tumor -had not yet been fully characterized or widely recognized in the literature at the time of diagnosis. In the remaining cases, the lack of distinctive histopathological features hindered a definitive diagnosis. In conclusion, according to our experience, DNA methylation profile analysis represents a very attractive diagnostic tool and provides important support for the diagnosis and classification of CNS tumors.

Paul Langerhans Jr. described under the microscope single cells and aggregates never seen before; he had broad interests and a non-ordinary biography. He died young from tuberculosis, but continued to study until the end, driven by curiosity and disregarding his fate. In him coexisted the genius of the discoverer and the diligence of the observer of nature.

Sarcoidosis is a systemic granulomatous disease of unknown etiology, characterized by the formation of non-necrotizing granulomas in various organs, with the lungs and mediastinal lymph nodes being the most commonly affected sites. "Scar sarcoidosis" refers to the rare phenomenon in which sarcoid granulomas develop in pre-existing scars, such as surgical scars, tattoos, or sites of previous skin trauma. We report two cases of patients who presented with sarcoid granulomas developing in previous scar sites. The first case involved a 37-year-old man with a prior diagnosis of stage II pulmonary sarcoidosis who later developed erythematous plaques over scarred areas. A skin biopsy confirmed non-necrotizing granulomas. The second case describes a 45-year-old woman who presented with erythematous-violaceous plaques over previous traumatic scars, with subsequent tests revealing systemic sarcoidosis. Scar sarcoidosis highlights the diverse clinical presentations of sarcoidosis, emphasizing the need for clinicians to be vigilant of new or unusual manifestations. Recognizing this form of sarcoidosis can facilitate early systemic diagnosis and impact patient management. These cases underscore the importance of a multidisciplinary approach in diagnosing and managing sarcoidosis, given its dynamic and unpredictable nature.