Histopathology最新文献

Aims: Mesothelioma (MESO) is a rare and aggressive tumour originating from mesothelial cells, primarily affecting the pleura and peritoneum. Its diagnosis remains challenging due to non-specific clinical, radiological and histopathological features, compounded by morphological diversity and overlapping immunohistochemical profiles with other tumours. Building on our previous finding that GFPT2 is highly expressed in MESO tissues, we evaluated its diagnostic utility in distinguishing MESO from histological mimics.

Methods and results: We conducted an immunohistochemical analysis of GFPT2 in 101 MESO cases and 266 histological mimics, including 100 non-small cell lung cancer (NSCLC), 40 high-grade serous ovarian cancer (HGSOC), 6 epithelioid hemangioendothelioma (EHE), 33 solitary fibrous tumour (SFT), 23 aggressive fibromatosis (AF), 6 synovial sarcoma (SS), 7 dedifferentiated liposarcoma (DDLPS), 6 leiomyosarcoma (LMS), 4 malignant peripheral nerve sheath tumour (MPNST), 8 sarcomatoid carcinoma, 20 reactive mesothelial hyperplasia (RMH) and 13 well-differentiated papillary mesothelial tumour (WDPMT) cases. GFPT2 positivity was detected in 85.15% (86/101) of MESO cases, significantly higher than in RMH (0%, 0/20), WDPMT (0%, 0/13), NSCLC (0%, 0/100), HGSOC (0%, 0/40), EHE (16.7%, 1/6), SFT (0%, 0/33), AF (21.74%, 5/23), SS (0%, 0/6), LMS (0%, 0/6), MPNST (25%, 1/4) and sarcomatoid carcinoma (12.5%, 1/8). However, DDLPS (85.7%, 6/7) showed high GFPT2 positivity.

Conclusions: This study demonstrates GFPT2's diagnostic utility in MESO, effectively overcoming tumour heterogeneity challenges. It distinguishes malignant mesothelial lesions from benign/borderline ones (RMH/WDPMT), differentiates epithelioid MESO from epithelioid malignances(NSCLC/HGSOC/EHE) and aids in sarcomatoid MESO versus spindle cell tumours (SFT/AF/SS/LMS/MPNST/sarcomatoid carcinoma), though limited for DDLPS. In summary, GFPT2 is a promising novel antibody demonstrating 85.2% sensitivity and 94.7% specificity.

Aims: Bone marrow (BM) biopsy is an important procedure in B-cell lymphoma staging. In most biopsies, the presence or absence of a lymphoma infiltrate can reliably be determined by standard histology. However, in a subset of cases with limited infiltration, this assessment remains inconclusive, requiring an alternative approach. Next-generation sequencing (NGS)-based detection of immunoglobulin (IG) gene rearrangements has the potential for resolving these difficult cases because of its high sensitivity. In this study, we tested the NGS-based IG clonality protocol developed by the EuroClonality-NGS Working Group on BM staging biopsies.

Methods and results: Forty-nine BM biopsies ranging from morphologically and immunohistochemically evidently involved to negative were analysed and compared to the original lymphoma. A clear distinction in the abundance of overlapping clonal IG rearrangements was observed between BM biopsies that were positive versus negative for lymphoma based on morphology and immunohistochemistry. In the 12 BM biopsies in which morphology and immunohistochemistry were insufficient to differentiate between the presence or absence of lymphoma, the estimated B-cell infiltration ranged from 1% to 5%. In these cases, NGS-based IG clonality analysis of paired primary lymphoma/BM biopsies provided a binary outcome; a subset of cases with hardly or no primary lymphoma-derived IG gene rearrangements in the BM biopsy could be distinguished from cases with clear presence of primary lymphoma-derived IG gene rearrangements.

Conclusions: Our data demonstrated that paired NGS-based IG clonality analysis of lymphoma and BM samples can be a valuable additional tool for difficult BM staging biopsies in patients with B-cell lymphoma.

Aims: Metaplastic alterations of oxyntic mucosa in autoimmune gastritis (AIG) remain under investigation. This study aimed to characterize pyloric gland-like and intestinal metaplasia (IM) in AIG and assess their origin and prognostic significance.

Methods: A retrospective analysis of 147 H. pylori-negative AIG gastric biopsies was conducted. Twenty cases underwent immunohistochemical staining for MUC5AC, MUC6 and TFF2, and double immunostaining for MUC6-CDX2, MUC5AC-CDX2 and TFF2-CDX2.

Results: Corpus mucosa showed pyloric gland-like metaplasia in 98.6% (145/147) and IM in 81.6% (120/147) of cases; IM was complete in 99.2% (119/120). Epithelial dysplasia was absent; one signet-ring cell carcinoma was identified. Most cases were OLGA stage II (92.5%) and OLGIM stage I (58.5%). Metaplastic pyloric-like glands expressed MUC6, the mucin of normal antral glands, but also MUC5AC, the mucin of gastric pits and surface epithelium, a combination congruent with a distinct metaplastic subtype. All cases exhibited biphenotypic gastric mucous cells co-expressing MUC5AC-CDX2 (median 4.8% of MUC5AC-positive cells) and MUC6-CDX2 (median 3.1% of MUC6-positive cells) in glands and surface/foveolar epithelium. Glands with a mixed cellular population showing mucinous, biphenotypic, intestinal and intermediate 'transition' features provided further evidence of intestinal trans-differentiation. TFF2 was present in 25% (5 cases), in few glandular cells without CDX2 co-expression.

Conclusions: Oxyntic mucosa metaplasia in AIG constitutes a complex phenomenon of successive phases of cellular plasticity characterized by the appearance of a distinct pyloric-like metaplastic subtype followed by intestinal trans-differentiation. The autoimmune metaplastic background appears non-carcinogenic regarding intestinal-type adenocarcinoma development.

Aims: Renal tumours with oncocytic morphology are among the most difficult to classify at renal mass biopsy (RMB), and a number of emerging entities with low-grade oncocytic morphology have been recently described. This study aimed to evaluate pathological concordance between RMB and subsequent nephrectomy or repeat biopsy for oncocytic renal neoplasms and to identify pathological factors contributing to diagnostic discordance, including the impact of evolving tumour classification.

Methods and results: We retrospectively reviewed 145 cases of oncocytic renal neoplasms diagnosed on RMB, including 114 with subsequent nephrectomy and 31 with repeat biopsy only. Overall concordance was 92.9% between RMB and nephrectomy and 96.7% between initial and repeat RMB. Concordance for oncocytoma at nephrectomy was lower (81.4%), likely reflecting selection bias, but was 100% in cases with repeat biopsy. Review of discordant cases (n = 9) revealed that 55% (5/9) were reclassified as emerging tumour entities, specifically low-grade oncocytic tumour (LOT) and eosinophilic vacuolated tumour (EVT). Additional discordant cases were due to heterogeneous tumour morphology in chromophobe renal cell carcinoma (ChRCC) and incomplete immunohistochemical work-up leading to misclassification of rarer renal cell carcinoma subtypes.

Conclusions: Despite inherent diagnostic challenges, there was overall good concordance between RMB and nephrectomy or subsequent biopsy for the diagnosis of oncocytic tumours. Recognition of emerging tumour entities may reduce diagnostic uncertainty, improve classification in challenging cases, and further improve diagnostic concordance over time. Nonetheless, limitations of RMB, particularly related to tumour heterogeneity, highlight the importance of integrating pathological, clinical, and radiologic data to inform patient management.

Aims: Ovarian Sertoli-Leydig cell tumor (SLCT) with heterologous rhabdomyosarcoma (RMS) is exceptionally rare. While the presence of heterologous elements in SLCT is highly predictive of an underlying DICER1 mutation, the molecular alterations in these tumors, including in SLCTs with heterologous RMS, remain largely unknown. In this study, we aimed to characterize the clinicopathologic features of these rare tumors, and in a subset of cases, we analyzed in detail their molecular changes to investigate potential recurrent and component-specific genetic alterations.

Methods and results: We report clinicopathologic features of 11 ovarian SLCTs with heterologous RMS (positivity for desmin and myogenin); 10 were in keeping with embryonal and 1 with pleomorphic RMS. The patients showed a bimodal age distribution: seven patients (64%) were aged 33 years or younger (mean 20) and four patients (36%) were aged 52 years or older (mean 60). All tumors were unilateral. In addition to the RMS components, 8 of 11 cases (73%) contained other heterologous elements, including gastrointestinal-type mucinous epithelium (5 cases) and immature cartilage (3 cases). Seven of 11 cases (64%) underwent next-generation sequencing analysis. All tumors tested molecularly (7/7, 100%) harbored hotspot DICER1 mutations. Of these, six cases (86%) also carried a second nonsense or frameshift loss-of-function DICER1 mutation. One case had only a p.D1810Y hotspot mutation and consisted of high-grade sarcoma with focal rhabdomyoblastic differentiation (focal expression of desmin and myogenin) in keeping with pleomorphic RMS; the pleomorphic sarcoma component also exhibited mutation-type p53 expression. In addition to DICER1 mutations, TERT c.-124C>T promoter (4 cases) or TP53 mutations (3 cases) were present in all cases and were mutually exclusive. Component-specific analysis in two cases revealed shared common DICER1 hotspot mutations in both the SLCT and RMS components, supporting a clonal origin. In 1 case, a TERT promoter c.-124C>T somatic mutation was present only in the RMS component. In the other case, the TERT promoter mutation was found in both components, while a BRAF p.V600E mutation was exclusive to the RMS component.

Conclusion: Our study demonstrates that the majority (86%) of SLCTs with heterologous RMS harbor double DICER1 mutations (a hotspot mutation and a nonsense or frameshift loss-of-function mutation), supporting the existing knowledge on DICER1 mutations associated with RMS heterologous elements, the presence of which should trigger genetic counselling. Our findings also suggest that molecular alterations other than DICER1, namely, TERT promoter and TP53 mutations, may contribute to component-specific oncogenic transformation.

RB1 was the first identified tumour suppressor gene, named for its crucial role in opposing retinoblastoma oncogenesis. The RB1 gene encodes the retinoblastoma protein pRB, which is a well-known negative regulator of the cell cycle. However, pRB also contributes to cell differentiation by restricting reprogramming and stem cell properties. Accordingly, RB1 inactivation in tumours can induce phenotypic modifications, contributing to tumour progression. Indeed, RB1 pathogenic alterations, either point mutations or deletions, leading to pRB loss of function are observed in 5% of all human cancers. Mutations are much more prevalent in some histologic subgroups, including retinoblastoma, spindle cell lipoma, neuroendocrine prostate cancer and small cell lung carcinoma. In such entities, molecular investigation of tumour samples and mechanistic studies strongly suggest that early RB1 inactivation contributes not only to dysregulation of cell cycle control, but also to the tumour cell phenotype. Among skin carcinomas, RB1 inactivation is the hallmark of primary cutaneous neuroendocrine carcinoma commonly known as Merkel cell carcinoma (MCC), but it has also been described in other tumours including a subset of squamous cell carcinomas, sebaceous carcinomas and the recently described Wnt/beta-catenin-activated non-pilomatrical carcinomas. In this context, we provide a brief overview of the contribution of RB1 inactivation to oncogenesis and tumour cell phenotypes in general and summarise current knowledge regarding RB1-deficient cutaneous carcinomas, highlighting the potential uses of RB1 pathway characterisation for diagnosis, prognosis and therapeutic purposes.

Approximately 50% of penile squamous cell carcinomas are of the usual (conventional) type, resembling their counterparts in the skin or other organs. The remaining half comprises a heterogeneous group of histological variants, some of which exhibit highly distinctive morphological features. Current classification models recognize more than 14 subtypes of penile squamous cell carcinoma. Pathological guidelines recommend histological subtyping of penile carcinomas in diagnostic reports. This practice is clinically significant because specific subtypes carry distinct prognostic implications. However, diagnostic challenges may arise in certain cases due to overlapping histological features. While most subtypes of penile intraepithelial neoplasia (PeIN) are readily identifiable, a subset of cases presents diagnostic challenges. A notable example is distinguishing benign condylomas from low grade minimally atypical warty PeIN. Among invasive carcinomas, the most significant diagnostic difficulties arise in classifying verruciform tumours, due to their overlapping morphological features. Warty carcinomas may simulate giant condylomas; verrucous carcinoma may simulate giant condylomas or Papillary NOS carcinomas. Conversely, this tumour may be confused with low grade warty carcinomas. With some experience, histological classification using H&E stain is possible in about 70% of the cases. The remainder 30%, however, presents diagnostic difficulties even for experienced pathologists. The use of immunostaining and HPV genotyping are crucial aids in the differential diagnosis. By describing and illustrating in detail their morphological features, suggesting treatment options, and emphasizing diagnostic difficulties in the differential diagnosis, we aimed to assist our colleagues in improving their penile neoplasia classification skills.

We focus in this review on the latest developments on several eosinophilic renal entities, aiming to provide an update on this topic that was previously addressed by the Genitourinary Pathology Society in their consensus papers on existing renal entities, and on novel, emerging, and provisional renal entities, and in the World Health Organization 2022 Classification of Renal Cell Tumours (5th Edition). The scope of this review includes an update on more recently described eosinophilic renal entities, including low-grade oncocytic renal tumour (LOT), eosinophilic vacuolated tumour (EVT), folliculin (FLCN) mutated tumour, succinate dehydrogenase (SDH)-deficient renal cell carcinoma, epithelioid angiomyolipoma/epithelioid PEComa (eAML/ePEComa), eosinophilic solid and cystic renal cell carcinoma (ESC RCC), anaplastic lymphoma kinase (ALK)-rearranged RCC, fumarate hydratase (FH)-deficient RCC, papillary renal neoplasm of reversed polarity (PRNRP), tubulocystic RCC (TC-RCC), and thyroid-like follicular carcinoma of kidney (TLFCK). These renal entities fall within the spectrum of eosinophilic renal tumours, in addition to the more common ones with eosinophilic features that will not be covered in this review, such as clear cell renal RCC, papillary RCC, chromophobe RCC, TFE3 rearranged RCC, and TFEB-altered RCC. Pathologists need to consider these less common renal entities in the differential of any eosinophilic renal tumour to be able to diagnose them for the benefit of their patients. The recent developments and acquired knowledge on newer renal entities with eosinophilic cytoplasm opened insights into the clinical, pathological, immunohistochemical, molecular, epidemiological aspects, and the prognosis of these entities. We emphasize the role of routine morphology, aided by appropriate and select immunohistochemistry, as essential keys for diagnosing eosinophilic renal tumours.