Histopathology最新文献

Aims: Evaluation of pathological complete response (pCR) [no residual invasive carcinoma in the breast (RIC) or lymph node metastases (LNM) in surgical specimens following therapy] is typically based on evaluation of one level of haematoxylin and eosin (H&E) section. Not achieving pCR is associated with worse outcomes, and additional therapy may ensue. This study of patients with triple-negative (TNBC) or human epidermal growth factor receptor 2 (HER2)-positive (HER2+) breast cancer who underwent neoadjuvant therapy aims to assess whether occult residual disease (ORD) can be identified in deeper sections of tumour beds and lymph nodes in cases originally reported as pCR and whether ORD is associated with worse outcomes.

Methods and results: In 84 cases of pCR (2009-17) at our institution, deeper-level recuts were assessed for ORD. Oncological and survival outcomes were compared. ORD was identified in seven of 40 TNBC (17.5%; five RIC; one LMN; one RIC and LMN) and four of 44 HER2+ (9.1%; three RIC; one LMN) cases (all residual cancer burden I). Median follow-up was 46.7 months for TNBC (one local recurrence, four distant metastases and two deaths) and 86.8 months for HER2+ (no local recurrence, three distant metastases and two deaths). All recurrence and death events occurred in patients with pCR without ORD, with no recurrence events in patients with ORD.

Conclusions: In patients with TNBC and HER2+ breast cancer with pCR by standard pathological assessment, occult residual disease is not uncommon. Occult disease was not associated with worse oncological or survival outcomes, suggesting standard pathological assessment is sufficient to identify clinically meaningful disease.

Aims: This study investigated the utility of combined p16 and p53 immunohistochemistry (IHC) for diagnosing high-risk human papillomavirus (HR HPV)-associated oral epithelial dysplasia (OED) and its associated clinical behaviour, including disease recurrence and transformation to malignancy.

Methods and results: The expression of p53 was evaluated in 105 cases of HR HPV-positive oral cavity OED, of which 104 were scored as positive for p16. HPV status was confirmed by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) for E6 mRNA or RNA in situ hybridization (ISH). Seven cases of p16-positive oral cavity OED with abnormal p53 expression and/or TP53 mutation and negative HPV RNA ISH were excluded. Most cases (93%) demonstrated classic HPV-associated basaloid morphology, and 7% were keratinizing. The most affected sites were the floor of the mouth/ventral tongue (61%), followed by the lateral tongue (18%) and gingiva (13%). p53 IHC showed that 76% of cases demonstrated a null-like / basal-sparing pattern, while 24% demonstrated a mid-epithelial/basal sparing pattern. Ten cases exhibited an invasive or suspicious for microinvasive component on biopsy. Dysplasia recurred in 14 cases, and a single case transformed to squamous cell carcinoma.

Conclusion: The combination of p16 positivity and a basal-sparing pattern of p53 is predictive of HR HPV in OED, eliminating the need for further HPV-specific testing. Although HPV OED may co-occur with invasive squamous cell carcinoma on biopsy, the transformation to malignancy is low.

Aims: Benign tumours of the rete testis include mostly cystadenomas and adenomas. A subset with tubular or tubulopapillary architecture shows morphological similarities to Sertoli cell tumours; these neoplasms were previously termed "Sertoliform cystadenomas of the rete testis". In the most recent WHO classification, they have been interpreted as Sertoli cell tumours, not otherwise specified (NOS), with pure intra-rete growth, and therefore excluded as an entity. The remaining cystadenomas of the rete testis vaguely resemble tumours of Mullerian origin arising in the ovaries. In this study we analyse benign tumours of the rete testis, including a subset with Sertoliform features.

Methods and results: Benign neoplasms of the rete testis were identified through query of consultation and institutional files. Clinicopathologic data were collected, and available slides were reviewed. Cases were assessed using IHC and three separate DNA sequencing panels. Eleven tumours from patients 32-78 years old were evaluated. Four were classified as Sertoliform adenomas/cystadenomas, displaying tubulo-papillary or tubular/trabecular architecture; all of them were PAX8-positive and lacked nuclear beta-catenin expression. The remaining seven tumours were benign cystadenomas NOS. Genomic analysis was performed successfully in 10/11 tumours (including all Sertoliform adenomas/cystadenomas) and revealed no pathogenic variants in CTNNB1, KRAS, or BRAF.

Conclusion: Sertoliform cystadenomas of the rete testis differ from Sertoli cell tumours NOS, as evidenced by the absence of molecular markers characteristic of Sertoli cell tumours. The remaining benign cystadenomas lack molecular alterations seen in Mullerian tumors of the ovaries.

Aims: Atypical ductal hyperplasia (ADH) in male breast tissue is a rare condition with limited understanding. We aimed to elucidate the clinicopathological characteristics of ADH in male patients, focusing on its prevalence, presentation, and associated factors.

Methods and results: We analysed 40 cases of ADH from 1626 male breast cases encountered between 2013 and 2023. Clinicopathological data were reviewed to identify key features and trends. The mean age of the patients in our cohort was 43 years. ADH was mainly discovered incidentally during the workup for gynecomastia in 85% (34/40) of cases. Only two cases, 5% (2/40), initially presented as a palpable mass; one was pure ADH and the other one an ADH with intraductal papilloma (IDP). Nipple discharge was the initial presentation in 7.5% (3/40) of cases, all of which were associated with IDP. Additionally, 5% (2/40) of cases were identified due to calcifications on imaging. Excision was the initial diagnostic procedure in 77.5% (31/40) of cases, and core needle biopsy (CNB) in 22.5% (9/40). In most patients 70% (28/40) had unilateral disease, while 84.4% (27/32) exhibited multifocal lesions, and 90.6% (29/32) showed cribriform architectural patterns. Notably, 77.3% (17/22) of patients had a history of medications linked to gynecomastia. During follow-up (9 months to 26 years), two patients developed ductal carcinoma in situ (DCIS).

Conclusion: ADH in male patients primarily presents incidentally alongside gynecomastia. Multifocality and cribriform patterns are common histological features. The association with medication-induced gynecomastia and the potential progression to DCIS highlight the clinical significance of ADH in males.

Aims: We compiled two cohorts of colorectal adenosquamous carcinoma (ASC) to describe its histologic and molecular aspects using modern parameters to compare them with literature reports using meta-analysis of cohorts and individual case series.

Methods and results: We identified 53 colorectal ASC from 19 North American academic medical centres, in addition to national database reports on 94 Dutch cases. We analysed available clinical, histologic, and immunohistochemical features and patient outcome. ASC comprised 0.02% of colorectal cancers in the Dutch database. The median cohort patient ages at resection were 65 and 69 years (North American and Dutch cohorts, respectively), with a roughly equal male:female ratio. The squamous component represented between 5% and 95% of each tumour, with a median of 50%. Tumour-infiltrating lymphocytes (TILs) were generally low (66%), and tumour budding was often Bd1 (64%). Most cases were pT3 (55%) or pT4 (40%), with nodal metastases in more than half (58%). Twenty-three cases (43%) metastasized distantly, most commonly to the liver. Mismatch repair (MMR) deficiency was identified in 34% of the cases. Follow-up was available for 48 patients; 13 (27%) had recurrent disease and 29 (60%) died. A total of 31 patients progressed, with median time to progression of 18 months. Available data for the Dutch cohort revealed largely similar findings, as did review of cases in the literature.

Conclusion: Colorectal ASC usually presents at an advanced stage. Despite high rates of MMR deficiency and low tumour budding, TILs were generally low, and there is a high recurrence rate and poor prognosis.

Aims: Intraductal carcinoma (IDC) is an independent pathological parameter for adverse prostate cancer (PCa) outcome. Although most IDC are believed to originate from retrograde spread of established PCa, rare IDC cases may represent precursor lesions. The actual transition areas between intraductal and invasive cancer, however, have not yet been identified. Our objective was to identify intraductal-invasive PCa transitions using 2- and 3-dimensional microscopy.

Methods and results: Seventy-five samples from 46 radical prostatectomies with PCa were immunohistochemically stained for basal cell keratins. In 35 samples, atypical glands that were indistinguishable from invasive adenocarcinoma (IAC) had focal 34BE12-positive basal cells. These IAC-like glands were present adjacent to IDC and prostatic intra-epithelial neoplasia (PIN) in 21 of 45 (46.7%) and 16 of 58 (27.6%) cases, respectively. Whole-mount confocal imaging of immunofluorescent Ker5/18 double-stained and cleared 1-mm-thick intact tissues revealed spatial continuity between IDC, IAC-like glands and IAC with a gradual loss of basal cells. In 24 of 35 (68.6%) samples more than one IAC-like focus (median 3.0) was present.

Conclusions: We identified areas of spatial transition between PIN, IDC and IAC, characterised by remnant basal cells in IAC-like glands. Based on the coexistence of IDC and PIN, the gradual loss of basal cells in IAC-like glands and IAC-like glands' multifocality, we propose a novel hypothesis on intraductal carcinogenesis, which we term 'repetitive invasion, precursor progression' (RIPP).

Aims: The current American Joint Committee on Cancer (AJCC) staging manual and the College of American Pathologists (CAP) colorectal carcinoma (CRC) protocol specify use of a four-tiered grading system (i.e. grades 1-4; well-differentiated-undifferentiated) for CRC, based on percentage of gland formation. The World Health Organization (WHO) 5th edition grades CRC into low-grade (well- and moderately differentiated) and high-grade (poorly and undifferentiated), based on the least differentiated component. We studied interobserver agreement and practice patterns among pathologists when grading CRC by these two grading systems.

Methods and results: Five gastrointestinal pathologists reviewed 100 scanned CRC slides and graded the tumour on each slide, per provided criteria in (a) WHO 5th edition book, (b) AJCC manual/CAP CRC protocol and (c) their clinical practice. A questionnaire for grading selected CRC subtypes was also provided. Statistical analysis was performed using Pearson's χ² test and Fleiss multi-rater kappa analyses. Overall, agreement among the five reviewers when grading via WHO and AJCC criteria for low-grade and high-grade CRC was moderate (κ = 0.568, P < 0.001) and good (κ = 0.611, P < 0.001), respectively. All reviewers graded significantly more tumours as high-grade when using WHO (median = 46) versus AJCC/CAP criteria (median = 20).

Conclusions: Interobserver agreement was higher using the AJCC grading criteria as a two-tiered system. Significantly more tumours were called high-grade using the WHO criteria. This raises concerns regarding upgrading tumours, as well as potential differences in grading tumours among pathologists worldwide, based on regional preferred grading systems. Synchronisation of these two grading systems is necessary for uniform grading of CRCs throughout institutions.

Aims: The number of orthotopic lung transplants (OLT) has skyrocketed since the 1960s, generating an ever-increasing cohort of post-OLT patients. Many challenges exist in the post-OLT timeframe, including donor graft dysfunction, infection, malignancy, and immunosuppression-related conditions. A rather elusive topic in the posttransplant setting remains the impact of the underlying disease process and donor lungs on other organ systems and the complications arising from the complex physiologic interactions. The liver represents a vital organ often impacted in many ways by the lung transplant procedure. Also, there is a higher likelihood of adverse outcomes in OLT recipients who have significant liver pathology. Yet little is known about the morphologic changes in liver after patients have received an OLT. In this study we retrospectively reviewed liver pathology cases obtained after the patient received an OLT.

Methods and results: Histology was reviewed by three pathologists and evaluated with a standardized checklist format. In our cohort, we found morphologic features of hepatic injury in the form of vascular outflow obstruction, nodular regenerative hyperplasia, portal vessel changes, and steatosis/steatohepatitis, but there was a striking absence of advanced fibrosis in our cohort.

Conclusion: Here we present the first comprehensive account of morphologic changes in livers of post-OLT patients. We believe that this information will aid clinical decision-making during monitoring of hepatic function and fibrosis in patients with OLT and other complex pulmonary diagnoses.