Assessing venous invasion in stage II colon cancer: optimal elastin stains and survival analysis.

AIMS: Venous invasion (VI) in colorectal carcinoma influences treatment strategies, especially in early stages. Despite elastin staining effectiveness in detecting VI, guidelines for its routine application, including the optimal number of slides for staining, are limited. METHODS: Elastin staining was performed for VI assessment in patients with colorectal adenocarcinoma. Patients were categorised into two groups: single elastin stain group (SEG, n=248) and multiple elastin stain group (MEG, n=204). RESULTS: The average number of elastin-stained blocks was 2±1.7, increasing to 3.3±1.9 in MEG. VI detection was significantly higher in patients in MEG (50.5%) compared with SEG (37.0%) (p=0.004). VI detection rate was higher in MEG (63.7%) than in SEG (46.0%) among patients with stage III-IV disease (p=0.011), but did not significantly differ among patients with stage I-II disease. Staining two blocks improved VI detection without additional gains from more stains. Compared with elastin performed on a single block, VI detected by elastin stain on two or more blocks did not significantly impact progression-free or disease-free survival with stage II patients. CONCLUSIONS: Employing two elastin stains on separate blocks significantly enhances VI detection in colorectal carcinoma without additional benefits from more extensive staining. This study suggests that while increasing sensitivity for VI detection, staining beyond two blocks may not benefit prognostication and could be counterproductive, warranting further research. We emphasise the need for strategic use of the elastin stain and cautious interpretation of the increased detection sensitivity of multiple elastin stains.

Impact of NOTCH1 expression in primary breast adenoid cystic carcinoma.

AIMS: Adenoid cystic carcinoma (AdCC) originates from salivary-type like glands in the head and neck, lung, and breast. AdCC shows chromosomal translocation, resulting in MYB::NFIB fusion and overexpression of MYB. Recently, NOTCH1 pathway alteration has been recognised in a subset of patients with salivary gland AdCC and has been shown to be associated with poor survival. In this study, we investigated the correlation of NOTCH1 pathway alteration with the clinical outcome of patients with primary breast AdCC by examining NOTCH1 immunoreactivity in attempts to better predict clinical outcomes. METHODS: We identified 25 cases of breast AdCC, reviewed the clinical outcome and performed immunohistochemical (IHC) staining for NOTCH1 on FFPE sections. RESULTS: IHC evaluation of NOTCH1 expression in 25 cases of primary breast AdCCs revealed a positive correlation between NOTCH1 expression and primary tumour size. All cases with NOTCH1 expression were greater than 15 mm in size at presentation but only 50% of NOTCH1 negative tumours were greater than 15 mm. We demonstrated a positive correlation between NOTCH1 positive AdCCs and recurrence/metastases. 63.6% of NOTCH1 positive AdCCs had either metastases or recurrence. On the contrary, only 21.5% of NOTCH1 negative AdCCs had recurrence or metastases. AdCCs with NOTCH1 positivity correlated with inferior relapse free survival (median 33 vs 129 months). CONCLUSIONS: Our study demonstrates that in patients with breast AdCC, overexpression of NOTCH1 ≥20% is associated with larger tumour size and aggressive clinical outcomes. Importantly, NOTCH1 inhibitors may have potential therapeutic effect in patients with breast AdCC.

Novel and unusual USP6 fusion partners in aneurysmal bone cyst and their role in pathogenesis and histopathological evaluation of this disease.

AIMS: The purpose of this study is to report novel and unusual USP6 fusion partners in aneurysmal bone cysts (ABCs). These findings may be useful in routine diagnostics as well as in studying the biology of USP6-related disorders. METHODS: A cohort of seven patients diagnosed with ABC examined between 2014 and 2023 at Motol University Hospital in Prague was included into this retrospective non-randomised study. All cases were analysed using histopathological evaluation, immunohistochemistry and Anchored multiplex RNA methods. Demographic characteristics and clinical data were also analysed. RESULTS: We identified two novel (ZFX and IP6K2), three unusual (MEF2A, EIF1 and COL1A2) and two common (CDH11) fusion partners with USP6 gene among all seven cases of ABC. CONCLUSIONS: Cases in our study were diagnosed as ABCs due to characteristic clinical and morphological presentation. However, not all cases are as self-evident, and molecular testing is necessary. The identification of these gene alterations can be useful in distinction between true ABC and ABC-like changes among many benign and malignant bone tumours.

PHOX2B: a diagnostic cornerstone in neurocristopathies and neuroblastomas.

Paired-like homeobox 2B (PHOX2B) is a gene essential in the development of the autonomic nervous system. PHOX2B mutations are associated with neurocristopathies-Hirschsprung disease (HSCR) and congenital central hypoventilation syndrome (CCHS)-and peripheral neuroblastic tumours. PHOXB2 plays an important role in the diagnostics of these conditions.Genotyping of a PHOX2B pathogenic variant is required to establish a diagnosis of CCHS. In HSCR patients, PHOX2B immunohistochemical staining has proven to be a valuable tool in identifying this disease. Furthermore, PHOXB2 is a predisposition gene for neuroblastoma, in which PHOX2B immunohistochemical staining can be used as a highly sensitive and specific diagnostic marker. The utility of PHOX2B immunohistochemistry in pheochromocytoma and paraganglioma has also been studied but yields conflicting results.In this review, an overview is given of PHOX2B, its associated diseases and the usefulness of PHOX2B immunohistochemistry as a diagnostic tool.

Macroscopic examination of gynaecological specimens: a critial and often underemphasised aspect of pathological reporting.

Pathological examination of surgical specimens and compilation of a surgical pathology report comprises a series of events which includes macroscopic examination and tissue sampling, either complete or selected. This step is critical but often overlooked in the literature and not given the attention it deserves. In this review, we discuss the macroscopic examination and grossing of gynaecological pathology specimens, with reference to national and international protocols. We provide guidance as to the degree of sampling necessary in different scenarios and stress that a common-sense approach is necessary with flexibility in the degree of sampling depending on a variety of factors.

Macroscopy of specimens from the head and neck.

Macroscopic examination of surgical resections from the head and neck may be difficult due to the complex anatomy of this area. Recognition of normal anatomical structures is essential for accurate assessment of the extent of a disease process. Communication with the surgical team, correct specimen orientation and sampling are critical for assessment and the importance of radiological and clinical correlation is emphasised. Tumour involvement at each subsite is highlighted with reference to where there are implications on pathological staging and the potential need for adjuvant therapy.

CT features based preoperative predictors of aggressive pathology for clinical T1 solid renal cell carcinoma and the development of nomogram model.

BACKGROUND: We aimed to identify preoperative predictors of aggressive pathology for cT1 solid renal cell carcinoma (RCC) by combining clinical features with qualitative and quantitative CT parameters, and developed a nomogram model. METHODS: We conducted a retrospective study of 776 cT1 solid RCC patients treated with partial nephrectomy (PN) or radical nephrectomy (RN) between 2018 and 2022. All patients underwent four-phase contrast-enhanced CT scans and the CT parameters were obtained by two experienced radiologists using region of interest (ROI). Aggressive pathology was defined as patients with nuclear grade III-IV; upstage to pT3a; type II papillary renal cell carcinoma (pRCC), collecting duct or renal medullary carcinoma, unclassified RCC or sarcomatoid/rhabdoid features. Univariate and multivariate logistic analyses were used to determine significant predictors and develop the nomogram model. To evaluate the accuracy and clinical utility of the nomogram model, we used the receiver operating characteristic (ROC) curve, calibration plot, decision curve analysis (DCA), risk stratification, and subgroup analysis. RESULTS: Of the 776 cT1 solid RCC patients, 250 (32.2%) had aggressive pathological features. The interclass correlation coefficient (ICC) of CT parameters accessed by two reviewers ranged from 0.758 to 0.982. Logistic regression analyses showed that neutrophil-to-lymphocyte ratio (NLR), distance to the collecting system, CT necrosis, tumor margin irregularity, peritumoral neovascularity, and RER-NP were independent predictive factors associated with aggressive pathology. We built the nomogram model using these significant variables, which had an area under the curve (AUC) of 0.854 in the ROC curve. CONCLUSIONS: Our research demonstrated that preoperative four-phase contrast-enhanced CT was critical for predicting aggressive pathology in cT1 solid RCC, and the constructed nomogram was useful in guiding patient treatment and postoperative follow-up.

Intrahepatic cholangiocarcinoma: histological diversity and the role of the pathologist.

Intrahepatic cholangiocarcinoma (iCCA) is one of the primary liver cancers and presents with tumor heterogeneity. About 50% of iCCAs comprise actionable mutations, which completely change patient management. In addition, the precise diagnosis of iCCA, including subtype, has become crucial, and pathologists play an important role in this regard. This review focuses on iCCA heterogeneity; looking at different perspectives to guide diagnosis and optimal treatment choice.

Dematiaceous fungal infections: clinical and pathologic conundrums.

Dematiaceous fungi are defined by pigment within their cell walls. They are increasingly recognised human pathogens, causing a wide range of clinical presentations, from localised subcutaneous infections to disseminated disease in rare cases. We report our institutional experience with diagnosis of dematiaceous fungal infections from 2005 to 2022 and highlight four instructive cases that clinically and pathologically mimicked other diseases for which the diagnosis was confirmed by fungal culture (one case) or supported by PCR with 28S rRNA and internal transcribed spacer primers (three cases). Two patients were immunocompromised and two had presumed exposure to the organism. In each highlighted case, fungal infection was not clinically suspected, and the pathologist was critical in making the diagnosis and ensuring appropriate clinical management, which was supplemented by fungal stains and novel molecular methods.

Clinicopathological analysis of BRAF and non-BRAF MAPK pathway-altered gliomas in paediatric and adult patients: a single-institution study of 40 patients.

AIMS: Mitogen-activated protein kinase (MAPK) pathway alteration is a major oncogenic driver in paediatric low-grade gliomas (LGG) and some adult gliomas, encompassing BRAF (most common) and non-BRAF alterations. The aim was to determine the frequency, molecular spectrum and clinicopathological features of MAPK-altered gliomas in paediatric and adult patients at our neuropathology site in Kuwait. METHODS: We retrospectively searched the data of molecularly sequenced gliomas between 2018 and 2023 for MAPK alterations, revised the pathology in view of the 2021 WHO classification and evaluated the clinicopathological data for possible correlations. RESULTS: Of 272 gliomas, 40 (15%) harboured a MAPK pathway alteration in 19 paediatric (median 9.6 years; 1.2-17.6) and 21 adult patients (median 37 years; 18.9-89.2), comprising 42% and 9% of paediatric and adult cases, respectively. Pilocytic astrocytoma and glioblastoma were the most frequent diagnoses in children (47%) and adults (43%), respectively. BRAF V600E (n=17, 43%) showed a wide distribution across age groups, locations and pathological diagnoses while KIAA1549::BRAF fusion (n=8, 20%) was spatially and histologically restricted to cerebellar paediatric LGGs. Non-V600E variants and BRAF amplifications accompanied other molecular aberrations in high-grade tumours. Non-BRAF MAPK alterations (n=8) included mutations and gene fusions involving FGFR1, NTRK2, NF1, ROS1 and MYB. Fusions included KANK1::NTRK2, GOPC::ROS1 (both infant hemispheric gliomas), FGFR1::TACC1 (diffuse LGG), MYB::QKI (angiocentric glioma) and BCR::NTRK2 (glioblastoma). Paradoxical H3 K27M/MAPK co-mutations were observed in two LGGs. CONCLUSION: The study provided insights into MAPK-altered gliomas in Kuwait highlighting the differences among paediatric and adult patients and providing a framework for planning therapeutic polices.

Gender distribution in surgical pathology journal publications and editorial boards.

AIMS: To investigate trends in representation of women among authors and editorial boards of surgical pathology journals over the last two decades.Secondary aims: to identify barriers and potential solutions. METHODS: The names and gender of first, middle, last authors and editorial board members were obtained from original articles from seven pathology journals from various geopolitical regions in 2002, 2011 and 2021. The proportion of women first, middle, last authors and editorial board members were compared over time. RESULTS: 1097 publications and 8012 individual authors were extracted. In 2002, 2011 and 2021, respectively, the percentage of women first authors were 28.3% (257 of 907), 31.9% (566 of 1773) and 41.1% (1421 of 3457); women middle authorship rates were 30.0% (159 of 530), 32.8% (375 of 1145) and 40.9% (1067 of 2609) and women last authors were 18.0% (34 of 188), 26.0% (82 of 315) and 36.0% (152 of 422). Women representation on editorial boards has increased (11.3%, 15.8%, 26.5%), but of the chief editors, there was only one woman in 2021, while all were men in 2002 and 2011. CONCLUSIONS: To our knowledge, this study is the first to document under-representation of women among authors and editorial boards of surgical pathology journals. While women representation has increased over time, predominance of men remains relative to workforce proportions. Our findings are comparable to those from other medical fields and prompt the need to investigate the underlying causes for this imbalance and implement strategies to promote diversity, equity and inclusion in academic surgical pathology.

Primary salivary duct carcinoma of the lung: clinicopathological features, diagnosis and practical challenges.

AIMS: To investigate the clinicopathological features, molecular characteristics and diagnostic criteria of primary salivary duct carcinoma of the lung (LSDC). METHODS: We analysed the clinicopathological and molecular features of five cases of LSDC retrieved from the archives of Shanghai Pulmonary Hospital from 2020 to 2022, and reviewed the relevant literature. RESULTS: All patients were men, with an average age of 66 years (age range: 49-79 years), and all lesions were central masses with a mean maximum diameter of 42.6 mm (range: 16-70 mm). Morphologically, LSDC comprised of intraductal and invasive components. Both the intraductal and invasive components of LSDC can exhibit papillary, micropapillary, cribriform, tubule structures and solid proliferation. The intraductal component can exhibit Roman bridge structures, which were usually accompanied by central comedo-like necrosis. Immunohistochemically, LSDCs consistently expressed cytokeratin (CK)7 (5 of 5) and showed variable positivity of androgen receptor (AR) (5 of 5) focally or diffusely; additionally, the tumour cells expressed human epidermal growth factor receptor 2 (HER2) (3+, n=3; 2+, n=2), GATA-binding protein 3 (3 of 5), and gross cystic disease fluid protein-15 (1 of 5), and all of which were negative for thyroid transcription factor-1, napsin A, p40, CK5/6 and p63. The residual basal/myoepithelial cells surrounding the in situ carcinoma expressed p40, CK5/6 and p63. TP53 mutation and HER2 gene amplification (3 of 5) were the most frequent genetic alterations in LSDC. All patients who underwent surgical lobectomies were alive without recurrence or metastasis. CONCLUSIONS: LSDC is a highly rare malignant tumour. The distinctive architecture of in situ carcinoma and tumour cells expressing AR can provide diagnostic indications for LSDC.

Macroscopic examination of pathology specimens: a critical reappraisal.

Meticulous macroscopic examination of specimens and tissue sampling are crucial for accurate histopathology reporting. However, macroscopy has generally received less attention than microscopy and may be delegated to relatively inexperienced practitioners with limited guidance and supervision. This introductory paper in the minisymposium, Macroscopy Under the Microscope, focuses on issues regarding macroscopic examination and tissue sampling that have been insufficiently addressed in the published literature. It highlights the importance of specimen examination and sampling, discusses some general principles, outlines challenges and suggests potential solutions. It is critical to get macroscopy right the first time as it may not be possible to rectify errors even with expert histological assessment or to retrospectively collect missing data after the specimen retention period. Dissectors must, therefore, receive adequate guidance and supervision until they are proficient in macroscopic specimen examination. We emphasise the importance of the clinical context, optimal specimen fixation, succinct and clinically relevant macroscopic descriptions, macrophotography and judicious tissue sampling. We note that current recommendations based on the number of blocks to be submitted per maximum tumour dimension are ambiguous as the amount of tissue submitted in a cassette is not standardised and it is unclear whether 'block' refers to a tissue block or a paraffin block. Concerns around potential oversampling of 'therapeutic' specimens that could result in overdiagnosis due to detection of incidentalomas are also discussed. We hope that the issues discussed in this paper will engender debate on this clinically critical aspect of pathology practice.

Schaumann bodies deposited along myenteric plexus of the muscularis propria is a unique histopathological feature of Crohn's disease.

AIMS: Schaumann bodies were first identified in sarcoidosis by Dr Schaumann in 1941. They were also detected in 10% of Crohn's disease (CD) cases in a study involving patients with surgically resected CD. However, the characteristics and significance of Schaumann bodies in CD have yet to be fully elucidated. This study aimed to determine the pathological features and diagnostic significance of Schaumann bodies in various bowel diseases. METHODS: Overall, 278 bowel specimens were collected from patients with CD, intestinal tuberculosis, ulcerative colitis, intestinal schistosomiasis, diverticulosis and idiopathic mesenteric vasculopathy. The frequency, pathology and clinical features of patients with Schaumann bodies were studied. RESULTS: Schaumann bodies were present exclusively in CD (27.0%, 38 of 141) and were not detected in other intestinal diseases within the series. In CD, Schaumann bodies were deposited along the myenteric plexus of the muscularis propria (84.2%, 32 of 38). These bodies were small (diameter: 60.3±32.7 µm) and exhibited a low density in the intestinal wall (1.1±0.4 per low-power field). The majority were located within the cytoplasm of multinucleated giant cells (84.2%, 32 of 38) and were not found within or adjacent to granulomas. Notably, the number of female patients with CD and Schaumann bodies was higher than that of males. CONCLUSION: Schaumann bodies are common in resected CD specimens, and their characteristic deposition pattern may serve as a diagnostic indication for CD.