Histopathology最新文献

Aims: The latest WHO edition proposed using a cut-off of ≥5% high-grade component (%HGc) as a criterion to label non-invasive papillary urothelial carcinomas as high-grade (pTaHG). It also suggested that tumours with minor high-grade component behave more indolently and are better labelled as mixed low- and high-grade papillary carcinomas.

Methods and results: We investigated the prognostic value of %HGc along with other clinical and morphological parameters. 130 pTaHGs and 96 pTaLGs were included. 9% and 12% of pTaHGs had ≤5% and ≤10% HGc, respectively. Anaplasia was present in six cases (5%), necrosis in 18 cases (14%) and CIS in 5 cases (4%). On average, the highest mitotic count per 1 HPF was 2.4 (range = 0-18), and the mean number of mitoses per 10 HPF was 9 (range: 0-93). The mean tumour diameter was 2.1 cm. Tumour multifocality was observed in 32 cases (25%). Among the histological parameters, only mitotic activity showed a correlation with the %HGc (P < 0.001). While recurrence was not significantly different between pTaLGs and pTaHGs (25% vs 35%; P = 0.09), stage progression was significantly different (0% vs 8%; P = 0.005). The two parameters that were associated with recurrence in pTaHGs were tumour multifocality and BCG therapy, while none was associated with progression. %HGc ≤5% and ≤ 10% did not correlate with lower rates of recurrence nor progression.

Conclusions: Those findings suggest that pTaHGs with minor HGc do not exhibit more indolent behaviour and should be approached similar to pTaLGs.

Aims: Tumour budding (TB) is a noteworthy morphologic indicator for tumour microenvironment (TME) especially because it is detectable with routine haematoxylin and eosin (H&E) staining. Its prognostic relevance has been demonstrated across various cancers, but its significance in pretreatment biopsy specimens of cervical cancer is unknown. This is the first study to investigate the prognostic value of TB in pretreatment cervical biopsy. Additional TME features identifiable with H&E such as cell nest size (CNS) were evaluated.

Methods and results: A retrospective review was conducted on the 2018 International Federation of Gynaecology and Obstetrics (FIGO) stage IIVA cervical cancer patients (N = 182) who had completed standard treatment. In multivariate analysis, TB (hazard ratio [HR], 2.06) and CNS (HR, 2.16) independently predicted overall survival. While TB (AUC, 0.7065) slightly outperformed CNS (AUC, 0.6975) in discriminating overall survival, the combination of TB and CNS demonstrated the highest performance (AUC, 0.7192) in time-dependent receiver operating characteristic analysis.

Conclusions: This study is the first to suggest TB in pretreatment biopsy specimens as a reliable morphologic prognosticator in cervical cancer. TME features may enhance precision oncology by offering insights into the individual tumour biology. The fact that these morphologic features are available from routine H&E slides, reserving immunohistochemistry or molecular analysis for indeterminate cases, is of particular value in low-resource settings where the burden of cervical cancer is most significant.

Background and objectives: GREB1-rearranged uterine tumours encompass a group of uterine mesenchymal tumours with varied histologic appearances. The fusion partners to GREB1 include NCOA1-3, SS18 and NR4A3. Given that some GREB1-rearranged uterine tumours exhibit histologic features of uterine tumours resembling ovarian sex cord tumour (UTROSCT), there is a general belief that GREB1-rearranged uterine mesenchymal tumours are part of the UTROSCT family.

Methods: In this study, we applied global DNA methylation and copy number analyses to a series of 10 GREB1-rearranged uterine tumours and 21 classic UTROSCTs (7 of which were molecularly confirmed to harbour ESR1::NCOA2/3 fusions).

Results: We found that GREB1-rearranged uterine tumors show an overlap in their global methylation profiles with UTROSCT, including ESR1::NCOA2/3 positive cases. Together, these tumours form a DNA methylation cluster separate from uterine smooth muscle tumours (leiomyomas and leiomyosarcomas), endometrial stromal sarcomas (low-grade and high-grade), embryonal rhabdomyosarcoma and SMARCA4-deficient uterine sarcomas. However, despite their epigenetic similarity, there were two notable differences. First, GREB1-rearranged uterine tumours as a group displayed a greater degree of genomic complexity with more extensive copy number alterations than conventional UTROSCTs, including those harbouring ESR1::NCOA2/3. Second, GREB1-rearranged uterine tumours frequently lacked overt sex cord morphology: while all 7 ESR1::NCOA2/3 UTROSCTs demonstrated corded, nested, trabecular and/or tubular/sertoliform patterns, only 1 GREB1-rearranged uterine tumour displayed a prominent trabecular pattern, with the remaining cases showing exclusively or predominantly diffuse/solid growth.

Conclusions: Overall, our findings confirm that GREB1-rearranged uterine tumours are part of the UTROSCT spectrum, though they frequently exhibit a more diffuse growth pattern and a higher degree of genomic instability.

Aims: Claudin-18 (CLDN18) is both a marker for the gastric phenotype and a therapeutic target. However, little is known about its immunoexpression in endocervical adenocarcinomas (ECAs), particularly as detected using the clone 43-14A antibody, or about the gene expression of its isoforms in ECAs.

Methods and results: We examined CLDN18, HIK1083, p16 and Rb expression by immunohistochemistry and high-risk human papillomavirus (HR-HPV) mRNA by in situ hybridization (ISH) in 121 ECAs, including 35 HPV-independent adenocarcinomas (gastric type [GAS], n = 24; non-GAS, n = 11) and 86 HPV-associated ECAs. We also analysed mRNA expression of the CLDN18.1 (lung type) and CLDN18.2 (gastric type) isoforms by quantitative polymerase chain reaction (qPCR) in selected cases. CLDN18 positivity was detected in 8/24 (33%) GASs, 0/11 (0%) non-GASs and 2/86 (2%) HPV-associated ECAs, with positivity defined as staining in ≥75% of tumour cells, as in gastric cancer. When a 5% cut-off was used, CLDN18 positivity was detected in 22/24 (92%) GASs, 0/11 (0%) non-GASs and 6/86 (7%) HPV-associated ECAs; CLDN18 expression was thus significantly associated with GAS histology (P < 0.0001). Among the 6 cases of HPV-associated ECAs with CLDN18 expression (ranging from 5% to 80%), the histological patterns included a mix of usual and mucinous features in 4 cases, pure usual type in 1 and villoglandular variant in 1. Otherwise features such as p16 overexpression and the Rb partial loss pattern were consistent with those of HPV-associated ECAs. Six of 22 (27%) CLDN18-positive GASs were also positive for p16, but their other features-such as CLDN18 expression and the Rb preserved pattern-were the same as in p16 negative GASs. Expression of CLDN18.2 mRNA but not CLDN18.1 mRNA was confirmed in both GASs and HPV-associated ECAs.

Conclusions: CLDN18 (43-14A) emerged as a potential diagnostic and therapeutic marker for GAS. A minor subset of HPV-associated ECAs also can be immunoreactive for CLDN18 and express CLDN18.2 mRNA, suggesting divergent gastric phenotypic differentiation. The caution is that GAS and HPV-associated ECAs can share overlapping histological features and similar expression of CLDN18 and p16.

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.