Histopathology最新文献

The grading and staging of liver biopsies from patients with steatotic liver disease, in particular metabolic dysfunction-associated steatotic liver disease (MASLD), is of fundamental importance in the execution of clinical trials of new therapeutic agents in this condition. Several semi-quantitative scoring systems have been designed for this purpose, of which the most used is the NASH Clinical Research Network (NASH CRN) system, in which the grade of disease is assessed on the severity of steatosis, hepatocyte ballooning and lobular inflammation. There has been recent interest in the role of portal inflammation (PI) in MASLD. The arguments for and against the inclusion of a semi-quantitative score for PI in grading MASLD activity are discussed in detail.

Mucin-producing breast lesions encompass a diverse range of entities with varied morphologies, distinct molecular genetics and different outcomes. Mucocele-like lesions (MLLs) are being increasingly recognised and sampled due to advancements in imaging techniques. These lesions can present with or without epithelial proliferation and atypia, which hold prognostic significance. Diagnosing MLLs on limited core needle biopsy (CNB) samples can be challenging. Mucinous breast carcinoma (MuBC) generally has an excellent prognosis in its pure form. Recent studies indicate that mucin-producing invasive cancers with micropapillary growth pattern, high nuclear grade or HER2 overexpression/amplification may not fare as well as their pure counterparts, suggesting that they should be distinguished from pure MuBCs. Invasive lobular carcinoma with extracellular mucin (ILCEM) is an emerging subtype of ILC characterised by neoplastic cells in cords, nests and trabeculae, often with signet ring morphology, floating in extracellular mucin. This can lead to misdiagnosis as a ductal phenotype due to varied architectural patterns or a MuBC due to the presence of extracellular mucin. This review highlights the spectrum of mucin-producing breast lesions, focusing on the above-mentioned entities along with recent molecular updates, potential mimics and diagnostic pitfalls on CNB specimens. Awareness of these entities, a practical approach to their diagnosis, combined with judicious use of immunohistochemistry, are crucial for accurate diagnosis by pathologists, which is in turn essential for guiding clinical decision making for optimal patient outcomes.

Aims: ASCL1, NEUROD1, POU2F3 and YAP1 are recently described markers of transcriptional subtypes in small cell lung carcinoma (SCLC), while DLL3, regulated by ASCL1, is a target of novel therapeutic agents in various neuroendocrine neoplasms. The expression of these markers in lung carcinoids is not well established.

Methods and results: We examined these markers in 109 lung carcinoids and compared their expression with that in 191 enteropancreatic neuroendocrine tumours (EP-NETs) and with lung carcinoid markers (OTP, TTF1). ASCL1, NEUROD1, OTP and TTF1 were positive in 56%, 0%, 84% and 35% of lung carcinoids, respectively. Of the OTP-negative lung carcinoids (n = 18), 4 (22%) were ASCL1-positive, of which one was TTF1-positive. In contrast, 59% of EP-NETs were NEUROD1-positive, whereas only rare tumours focally expressed ASCL1 (1.1%) and OTP (0.5%) and none expressed TTF1. DLL3 was positive in 57 (52%) lung carcinoids versus 5 (2.6%) EP-NETs. All lung carcinoids and EP-NETs were completely negative for POU2F3 and YAP1. We also analysed clinicopathologic correlates of ASCL1, OTP, TTF1 and DLL3 expression in lung carcinoids, expanding on several previously suggested associations, including ASCL1 and TTF1 with peripheral location, OTP with low Ki67 (P = 0.002) and low stage (P = 0.002) and DLL3 with high Ki67 (P = 0.002).

Conclusion: Unlike SCLC, lung carcinoids and EP-NETs completely lack the expression of POU2F3 and YAP1, which offers diagnostic applications. Our findings also nominate ASCL1 and NEUROD1 as site of origin markers for lung versus digestive NETs/carcinoids, respectively. Finally, the divergent expression of DLL3 in lung carcinoids and EP-NETs has therapeutic implications.

Aims: This study aimed to investigate the clinical and histopathological features of sebaceous tumours of the genital area and their association with human papilloma virus (HPV) infection and mismatch repair (MMR) protein deficiency.

Methods and results: Ethical approval was obtained, haematoxylin and eosin (H&E)-stained sections were reviewed, and immunohistochemistry (IHC) for p16, p53, mismatch repair proteins and HPV RNA-in-situ hybridization or HPV genotyping were performed. Clinical follow-up was retrieved from patient records. Six tumours presented in adulthood (median: 69; range: 48-73 years; M:F = 2:1) and were located on the penis, mons pubis and labia majora (median size 1.3 cm). There were four sebaceous carcinomas, one sebaceoma and one sebaceous adenoma. Three of four sebaceous carcinomas showing an overlying in-situ component were positive for high-risk HPV-ISH or subtypes, p16 block positive and p53 wild-type by IHC. The sebaceous adenoma showed loss of mismatch repair proteins and was associated with Muir-Torre syndrome (MTS), while all remaining tumours showed intact MMR protein staining, were negative for HPV, and p16 and p53 wildtype by IHC. The patient with MTS died of oesophageal adenocarcinoma; all other patients were alive without recurrences (median follow-up: 16 months, range 7-60 months).

Conclusions: In conclusion, the study emphasizes a pathogenetic role of HPV in genital sebaceous carcinomas that typically present with an in-situ component.

Aims: Fibrolamellar carcinoma (FLC) is a rare primary liver cancer. Adequate diagnosis is essential for appropriate treatment. The current study evaluates the diagnosis of fibrolamellar carcinoma in a Dutch cohort.

Methods and results: Adult patients diagnosed with FLC between 1990 and 2020, with pathology slides and clinical data available, were included. Two expert hepatopathologists revised all slides, including CD68 and CK7 stainings. In total, 54 adult patients diagnosed with FLC were included. Biopsies were available for 31 patients (57%) and resection or transplantation specimens in 23 patients (43%). Upon expert review, in nine patients (17%), the diagnosis of FLC was unequivocally confirmed. Four additional lesions harboured characteristics of both FLC and conventional hepatocellular carcinoma (HCC). Three patients exhibited histomorphological features suggestive of FLC, yet with negative CD68 staining. In the remaining 38 patients, the diagnosis was revised to intrahepatic cholangiocarcinoma (iCCA, n = 7, 13%), combined HCC/iCCA (n = 5, 9.3%) and conventional HCC (n = 26, 48%, of which 11 were steatohepatitic and 10 scirrhous subtypes).

Conclusions: The presence of extensive fibrosis in both iCCA and conventional HCC may result in misdiagnosis of FLC, in particular for the steatohepatitic and scirrhous variants of HCC. Misdiagnosis has important treatment consequences, as evidence supporting the efficacy of systemic treatments for FLC remains limited and extensive resection is the only curative option. Our Dutch historical cohort underlines the challenging diagnosis of FLC and emphasizes the critical role of expert review in accurate diagnosis.

Aims: The incidence and mortality rates of colorectal cancer (CRC) are increasing worldwide. We aimed to construct a novel classification system, Risk Score, based on the histopathological tumour microenvironment and assess its prognostic value in primary operable CRC.

Methods and results: Patients with stage I-III CRC who underwent radical resection between January 2020 and September 2021 were recruited. Eligible patients were randomized in a 1:1 ratio into a training cohort and a validation cohort. Tumour budding, tumour-stromal type, tumour-infiltrating lymphocytes, and tumour-stroma ratio were evaluated using the H&E sections of all excised specimens. The Risk Score was then developed on the basis of these four histopathological features, and its prognostic value was analysed. In the training cohort, patients with a high-Risk Score had shorter disease-free survival (DFS; HR 2.58, 95% CI: 1.78-3.72, P < 0.001) and overall survival (OS; HR 2.85, 95% CI: 1.74-4.67, P < 0.001) compared with those with a low Risk Score. Multivariate analysis revealed that the Risk Score remained an independent prognostic indicator of DFS and OS. These findings were confirmed in the validation cohort. A nomogram integrating all independent variables was also established to predict the individual risk of recurrence.

Conclusion: In this study, we developed a prognostic model to accurately predict disease progression and mortality in operable CRC and to guide adjuvant chemotherapy.

Aims: Tall cell carcinomas with reversed polarity (TCCRPs) are rare, indolent triple negative or oestrogen receptor (ER)-low positive breast cancers classically characterized by solid-papillary and papillary proliferations of eosinophilic columnar cells with reversed nuclear polarity. IDH2 R172 mutations are key oncogenic drivers in the majority of TCCRPs, exemplary of genotype-phenotype correlation among breast tumours. Other extramammary tumour types with IDH2 mutations can alternatively harbour analogous mutually exclusive IDH1 R132 mutations that appear to have similar effects on genome methylation, cellular differentiation and tumorigenesis. A prior report of a single IDH1-mutated TCCRP suggests extension of the IDH1/2 dichotomy to TCCRPs, but such exceedingly rare tumours have not been further characterized.

Methods and results: We identified two cases of TCCRP with IDH1 R132C mutation presenting in postmenopausal females and herein detail their clinical, histomorphologic, immunophenotypic and genetic features. The tumours showed disparate histologic features, with one ER-positive case closely mimicking an intraductal papilloma with florid usual ductal hyperplasia (UDH) and the other triple negative case demonstrating more classic features of TCCRP. The immunoprofiles in both cases were similar to TCCRP with IDH2 mutation. By targeted next-generation sequencing, both tumours harboured IDH1 R132C and PIK3CA H1047R mutations. Both patients underwent surgical excision without radiation therapy and were without disease at last follow-up.

Conclusions: This study expands the genetic and morphologic repertoire of TCCRP with implications and pitfalls for accurate diagnosis. The findings highlight the IDH1/IDH2 dichotomy with convergence of phenotype in these rare breast tumours.

Aims: Tubular adenoma of the breast (TAB) is a rare and understudied neoplasm, initially thought to represent a fibroadenoma (FA) variant. Recently, it has been shown that TABs lack MED12 mutations indicating a distinct pathogenesis, and an association between multiple TABs and Cowden syndrome (CS) has been described. We sought to evaluate PTEN status in TABs with immunohistochemistry (IHC) and identify other potential molecular alterations.

Methods and results: Forty-nine TABs from 43 patients (3 with CS, 40 without known CS) were retrieved. All patients were female, and ages ranged from 15 to 54 years old (median: 25). All TABs were well circumscribed and composed of closely packed, bilayered tubules with minimal intervening stroma. CS patients had multiple, bilateral TABs. PTEN IHC showed loss of expression in the luminal cells in TABs from all CS patients while the expression was retained in sporadic/non-CS TABs. Whole exome and/or Sanger sequencing was performed on 34 sporadic TABs and identified somatic missense mutations at codon 95 of the beta-actin gene, ACTB, in 19 cases (56%). No pathogenic MED12 mutations were identified in 29 TABs with next-generation sequencing results.

Conclusions: Overall, our findings highlight recurrent somatic ACTB mutations in more than half of sporadic TABs. CS-associated TABs but not sporadic TABs showed loss of PTEN expression. The presence of bilateral and/or multiple TABs should prompt PTEN IHC to rule out the possibility of CS.

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.