Histopathology最新文献

Invasive breast carcinomas with papillary features (IBCP) constitute a distinct and morphologically diverse group of breast cancers characterised by varying degrees of papillary architecture and invasive behaviour. IBCP encompass (1) papillary carcinoma in situ associated with invasion, (2) invasive solid papillary carcinoma (ISPC), (3) encapsulated papillary carcinoma (EPC)-like invasive carcinoma, (4) Papillary DCIS-like invasive carcinoma, (5) high-grade carcinomas with EPC-like or SPC-like morphology, and (6) invasive papillary carcinoma not otherwise specified (IPC), including the tubulopapillary pattern. This review summarises the evolving classification, histopathological features, diagnostic criteria, differential diagnoses, clinical prognosis, and treatment implications of various subtypes of IBCP. Particular attention is given to the diagnostic challenges and clinical relevance of recognising these tumour types. Standardised diagnostic criteria and further research into the biological behaviour of these entities are essential to guide appropriate management and improve prognostication.

Aims: Papillary renal cell carcinoma (pRCC) accounts for 15%-20% of RCC cases and is the second most common histologic subtype of RCC. In contrast to other common RCC subtypes, there continues to be ongoing debate about how to classify RCCs with papillary architecture and eosinophilic cytoplasm given the heterogeneity of histologic, IHC and molecular findings. Our study set out to characterize the histologic features and molecular alterations in cases that were originally diagnosed as pRCC, Type 2 or high-grade pRCC in a single institutional study (n = 63).

Methods and results: Histologically, the vast majority of the cases had a papillary pattern (n = 59). There were three cases that had a mixed solid and papillary pattern and one case that had a sarcomatoid architectural pattern. The cases were composed of large cells with eosinophilic cytoplasm, pseudostratified or apically oriented nuclei and prominent nucleoli. Molecular analysis of these cases revealed a wide range of genes that were mutated, with the most common ones being SETD2 (n = 9), PBRM1 (n = 5), KDM6A (n = 7), PMS2 (n = 4), NF2 (n = 7) and TERT (n = 7). Our study further identified cases that had molecular mutations in the RTK/RAS pathway (KRAS and NRAS), PI3K pathway (TSC2), TP53 pathway (TP53 and CHEK2) and copy number alterations in the cell cycle pathway (CDKN2A and CCND3).

Conclusions: These findings highlight the need to molecularly characterize these lesions as there is no specific histologic finding to identify cases that harbour different pathogenic alterations in specific genes.

Aims: Encapsulated papillary carcinoma (EPC) is characterized by neoplastic epithelial cells of low-to-intermediate nuclear grade arranged along fibrovascular cores. Classical EPC typically expresses oestrogen receptor (ER) and usually progesterone receptor (PR), while lacking human epidermal growth factor receptor 2 (HER2) overexpression and gene amplification. In contrast, apocrine encapsulated papillary carcinoma (AEPC), an exceptionally rare tumour with only a few well-characterized cases, exhibits a triple-negative phenotype (ER-, PR-, HER2-). The purpose of this study is to investigate whether the clinicopathological characteristics of AEPC differ from those of classical EPC.

Methods: Since 2014, 28 cases of AEPC have been identified at the Department of Pathology, Fudan University Shanghai Cancer Centre. We conducted a comprehensive clinicopathological evaluation and prognostic assessment in this case series.

Results: All 28 patients in our study were female, with a median age at diagnosis of 61.5 years (range: 34-90). Fifteen cases were consultation referrals, while 13 cases were diagnosed and treated at our centre. Histologically, all AEPC cases demonstrated cystic architecture with papillary growth patterns. The papillary structures were lined by cells exhibiting uniform apocrine differentiation. The degree of cellular atypia ranged from mild-to-moderate, with no severe atypia identified. Notably, myoepithelial cells were absent in both the papillary structures and lesion peripheries. Among the 28 AEPC cases, 18 were non-invasive, 8 demonstrated microinvasion (<1 mm), and 2 exhibited frank invasion (1-4 mm). The tumour cells exhibited a triple-negative profile and most cases presented with diffuse positivity for androgen receptor (AR) and gross cystic disease fluid protein 15 (GCDFP15). The median Ki-67 proliferation index was 10% (range: 5%-20%). Among the 28 patients, 19 received no adjuvant therapy, while 9 underwent postoperative radiotherapy and/or chemotherapy. With a median follow-up of 44.3 months (range: 7.4-135.5 months) for 27 patients, no recurrences or metastases were observed.

Conclusion: Classical EPC typically demonstrates favourable prognosis and is managed as ductal carcinoma in situ. In our study, none of the AEPC patients developed recurrence or metastasis, regardless of adjuvant therapy administration. Although AEPC exhibits a triple-negative immunophenotype, it differs biologically from conventional triple-negative breast cancer (TNBC). The indolent behaviour of AEPC aligns more closely with classical EPC rather than TNBC. Therefore, it may be more appropriate to treat AEPC patients using the same strategies applied to classical EPC.

Aims: Biomarkers are needed to identify patients with favourable-risk prostate cancers who could benefit from treatment versus active surveillance (AS). MRI-targeted biopsies may allow for better sampling of the 'dominant' tumour and therefore more accurate risk stratification. We evaluated ERG fusions and PTEN loss for predicting subsequent grade reclassification (GR) in a multiparametric MRI-screened cohort, comparing results in systematic versus targeted biopsies.

Methods and results: Validated immunohistochemistry assays for ERG and PTEN were performed on all cancer-containing cores of early AS biopsies, in a cohort of 127 Grade Group (GG) 1 AS patients with targeted and systematic biopsies. ERG fusions were identified in 43% of the cohort- 24% of these cases exhibited heterogeneous (subclonal or multi-clonal) ERG expression in sampled tumour. PTEN loss was identified in 16% of the cohort and all cases were heterogeneous. Neither ERG fusions nor PTEN loss were more likely to be found in targeted versus systematic cores. On multivariable Cox proportional hazard regression, PTEN loss was associated with extreme GR on subsequent biopsy (to GG ≥3) (hazard ratio [HR] 9.27, 95% confidence interval [CI] 2.10-40.9, P = 0.003) but ERG fusion was not (HR 2.82, CI 0.73-10.9, P = 0.13). PTEN loss was most strongly associated with this outcome when measured in systematic biopsy cores.

Conclusions: Frequent ERG heterogeneity suggests prevalent multiclonal disease in MRI-visible low-risk prostate cancers. Higher risk AS patients might benefit from PTEN loss evaluation to predict extreme GR, in both targeted and systematic biopsies, since targeted biopsies were not more likely to identify PTEN loss.

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.