The early detection and grading of dysplasia is the current standard of care to minimize mortality from colorectal cancer (CRC) in patients with inflammatory bowel disease. With the development of advanced endoscopic resection techniques, colectomy is now reserved for patients with invisible/flat dysplasia (either high-grade [HGD] or multifocal low-grade dysplasia) or endoscopically unresectable lesions. Although most pathologists are familiar with the morphologic criteria of conventional (intestinal type) dysplasia, the most well-recognized form of dysplasia, an increasing number of diagnostic material has led to the recognition of several different morphologic patterns of epithelial dysplasia. The term “non-conventional” dysplasia has been coined to describe these changes, but to date, the recognition and full appreciation of these novel forms of dysplasia by practicing pathologists is uneven. The recognition of these non-conventional subtypes is becoming increasingly important, as some of them appear to have a higher risk of developing HGD or CRC than conventional dysplasia or sporadic adenomas. This review describes the morphologic characteristics of all seven non-conventional subtypes that have been reported to date as well as our current understanding of their clinicopathologic and molecular features that distinguish them from conventional dysplasia or sporadic adenomas.
Citations
Citations to this article as recorded by
And the story goes on: non-conventional dysplasia of the colorectum Lavisha S. Punjabi, Yi Neng Lai, Anjula Thomas Journal of Pathology and Translational Medicine.2022; 56(2): 109. CrossRef
Clinicopathologic features of undetected dysplasia found in total colectomy or proctocolectomy specimens of patients with inflammatory bowel disease Dorukhan Bahceci, Gregory Y Lauwers, Won‐Tak Choi Histopathology.2022; 81(2): 183. CrossRef
Increased Risk of Non-conventional and Invisible Dysplasias in Patients with Primary Sclerosing Cholangitis and Inflammatory Bowel Disease Ruth Zhang, Gregory Y Lauwers, Won-Tak Choi Journal of Crohn's and Colitis.2022; 16(12): 1825. CrossRef
Increased histologic inflammation is an independent risk factor for nonconventional dysplasia in ulcerative colitis Eric D. Nguyen, Dongliang Wang, Gregory Y. Lauwers, Won‐Tak Choi Histopathology.2022; 81(5): 644. CrossRef
Background Urothelial carcinoma (UC) accounts for roughly 90% of bladder cancer, and has a high propensity for diverse differentiation. Recently, certain histologic variants of UC have been recognized to be associated with unfavorable clinical outcomes. Several UC studies have also suggested that tumor budding is a poor prognostic marker. Distant metastasis of UC after radical cystectomy is not uncommon. However, these metastatic lesions are not routinely confirmed with histology.
Methods We investigated the histopathologic features of 13 cases of UC with biopsy-proven distant metastases, with a special emphasis on histologic variants and tumor budding.
Results Lymph nodes (6/13, 46%) were the most common metastatic sites, followed by the lung (4/13, 31%), liver (4/13, 31%), and the adrenal gland (2/13, 15%). The histologic variants including squamous (n=1), micropapillary (n=4), and plasmacytoid (n=1) variants in five cases of UC. Most histologic variants (4/5, 80%) of primary UCs appeared in the metastatic lesions. In contrast, high-grade tumor budding was detected in six cases (46%), including one case of non-muscle invasive UC. Our study demonstrates that histologic variants are not uncommonly detected in distant metastatic UCs. Most histologic variants seen in primary UCs persist in the distant metastatic lesions. In addition, high-grade tumor budding, which occurs frequently in primary tumors, may contribute to the development of distant metastasis.
Conclusions Therefore, assessing the presence or absence of histologic variants and tumor budding in UCs of the urinary bladder, even in non-muscle invasive UCs, may be useful to predict distant metastasis.
Background CDKN2A is a tumor suppressor gene that encodes the cell cycle inhibitor protein p16. Homozygous deletion of the CDKN2A gene has been associated with shortened survival in isocitrate dehydrogenase (IDH)–mutant gliomas. This study aimed to analyze the prognostic value of p16 and to evaluate whether p16 immunohistochemical staining could be used as a prognostic marker to replace CDKN2A genotyping in diffuse gliomas.
Methods p16 immunohistochemistry was performed on tissue microarrays of 326 diffuse gliomas with diagnoses that reflected IDH-mutations and 1p/19q codeletion status. The results were divided into three groups (negative, focal expression, overexpression) according to the presence and degree of p16 expression. Survival analysis was performed to assess the prognostic value of p16 expression.
Results A loss of p16 expression predicted a significantly worse outcome in all glioma patients (n=326, p<.001), in the IDH-mutant glioma patients (n=103, p=.010), and in the IDH-mutant astrocytoma patients (n=73, p=.032). However, loss of p16 expression did not predict the outcome in the IDH-wildtype glioma patients (n=223, p=.121) or in the oligodendroglial tumor patients with the IDH-mutation and 1p/19q codeletion (n=30, p=.457). Multivariate analysis showed the association was still significant in the IDH-mutant glioma patients (p=.008; hazard ratio [HR], 2.637; 95% confidence interval [CI], 1.295 to 5.372) and in the IDH-mutant astrocytoma patients (p=.001; HR, 3.586; 95% CI, 1.649 to 7.801). Interestingly, patients who presented with tumors with p16 overexpression also had shorter survival times than did patients with tumors with p16 focal expression in the whole glioma (p< .001) and in IDH-mutant glioma groups. (p=.046).
Conclusions This study suggests that detection of p16 expression by immunohistochemistry can be used as a useful surrogate test to predict prognosis, especially in IDH-mutant astrocytoma patients.
Citations
Citations to this article as recorded by
Sporadic and Lynch syndrome-associated mismatch repair-deficient brain tumors Hyunhee Kim, Ka Young Lim, Jin Woo Park, Jeongwan Kang, Jae Kyung Won, Kwanghoon Lee, Yumi Shim, Chul-Kee Park, Seung-Ki Kim, Seung-Hong Choi, Tae Min Kim, Hongseok Yun, Sung-Hye Park Laboratory Investigation.2022; 102(2): 160. CrossRef
Simple approach for the histomolecular diagnosis of central nervous system gliomas based on 2021 World Health Organization Classification Maher Kurdi, Rana H Moshref, Yousef Katib, Eyad Faizo, Ahmed A Najjar, Basem Bahakeem, Ahmed K Bamaga World Journal of Clinical Oncology.2022; 13(7): 567. CrossRef
P16INK4A—More Than a Senescence Marker Hasan Safwan-Zaiter, Nicole Wagner, Kay-Dietrich Wagner Life.2022; 12(9): 1332. CrossRef
Background Langerhans cell histiocytosis (LCH) is more common in children than adults and involves many organs. In children, the BRAF V600E mutation is associated with recurrent and high-risk LCH.
Methods We collected paraffin blocks of 94 pediatric LCH patients to detect BRAF V600E mutation by sequencing. The relationship between BRAF V600E status and clinicopathological parameters were also critically analyzed.
Results BRAF V600E mutation exon 15 was detected in 45 cases (47.9%). Multiple systems LCH showed a significantly higher BRAF V600E mutation rate than a single system (p=.001). No statistical significance was evident for other clinical characteristics such as age, sex, location, risk organs involvement, and CD1a expression.
Conclusions In Vietnamese LCH children, the proportion of BRAF V600E mutational status was relatively high and related to multiple systems.
Background Patients with hereditary diffuse gastric cancer often undergo prophylactic gastrectomy to minimize cancer risk. Because intramucosal poorly cohesive carcinomas in this setting are typically not grossly visible, many pathologists assess the entire gastrectomy specimen microscopically. With 150 or more slides per case, this is a major time burden for pathologists. This study utilizes deep learning methods to analyze digitized slides and detect regions of carcinoma.
Methods Prophylactic gastrectomy specimens from seven patients with germline CDH1 mutations were analyzed (five for training/validation and two for testing, with a total of 133 tumor foci). All hematoxylin and eosin slides containing cancer foci were digitally scanned, and patches of size 256×256 pixels were randomly extracted from regions of cancer as well as from regions of normal background tissue, resulting in 15,851 images for training/validation and 970 images for testing. A model with DenseNet-169 architecture was trained for 150 epochs, then evaluated on images from the test set. External validation was conducted on 814 images scanned at an outside institution.
Results On individual patches, the trained model achieved a receiver operating characteristic (ROC) area under the curve (AUC) of 0.9986. This enabled it to maintain a sensitivity of 90% with a false-positive rate of less than 0.1%. On the external validation dataset, the model achieved a similar ROC AUC of 0.9984. On whole slide images, the network detected 100% of tumor foci and correctly eliminated an average of 99.9% of the non-cancer slide area from consideration.
Conclusions Overall, our model shows encouraging progress towards computer-assisted diagnosis of hereditary diffuse gastric cancer.
Citations
Citations to this article as recorded by
Artificial intelligence applicated in gastric cancer: A bibliometric and visual analysis via CiteSpace Guoyang Zhang, Jingjing Song, Zongfeng Feng, Wentao Zhao, Pan Huang, Li Liu, Yang Zhang, Xufeng Su, Yukang Wu, Yi Cao, Zhengrong Li, Zhigang Jie Frontiers in Oncology.2023;[Epub] CrossRef
Using Deep Learning to Predict Final HER2 Status in Invasive Breast Cancers That are Equivocal (2+) by Immunohistochemistry Sean A. Rasmussen, Valerie J. Taylor, Alexi P. Surette, Penny J. Barnes, Gillian C. Bethune Applied Immunohistochemistry & Molecular Morphology.2022; 30(10): 668. CrossRef
Background MicroRNA-552 (miR-552) has been reported to correlate with the development and progression of various cancers, including colorectal cancer (CRC). This study aimed to investigate miR-552 expression in cancer tissue samples compared to normal mucosal tissue and its role as a diagnostic or prognostic marker in CRC patients.
Methods Normal mucosal tissues and primary cancer tissues from 80 surgically resected CRC specimens were used. Quantitative real-time polymerase chain reaction was performed for miR-552 and U6 small nuclear RNA to analyze miR-552 expression and its clinicopathological significance. Immunohistochemistry for p53 and phosphatase and tension homolog (PTEN) was performed to evaluate their association with miR-552 expression.
Results miR-552 expression was significantly higher in primary cancer tissues compared to normal mucosal tissues (p<.001). The expression level of miR552 was inversely correlated with that of PTEN (p=.068) and p53 (p=.004). Survival analysis showed that high miR-552 expression was associated with worse prognosis but this was not statistically significant (p=.255). However, patients with CRC having high miR-552 expression and loss of PTEN expression had significantly worse prognosis than others (p=.029).
Conclusions Our results suggest that high miR-552 expression might be a potential diagnostic biomarker for CRC, and its combined analysis with PTEN expression can possibly be used as a prognostic marker.
Citations
Citations to this article as recorded by
Integration of TE Induces Cancer Specific Alternative Splicing Events Woo Ryung Kim, Eun Gyung Park, Yun Ju Lee, Woo Hyeon Bae, Du Hyeong Lee, Heui-Soo Kim International Journal of Molecular Sciences.2022; 23(18): 10918. CrossRef
Salivary gland tumors are histologically diverse, and each entity has distinctive histopathological and molecular features. We report two cases of salivary gland tumors with unique histological and molecular findings, which have not been documented previously. The tumors were located in the base of the tongue in both patients. Most tumor cells were arranged in cords and nests, giving a trabecularlike appearance. Focally, glandular structures with intraluminal mucin and perivascular pseudorosette-like configurations were identified. Tumor cells had eosinophilic to clear cytoplasm, and showed mild nuclear atypia. They were positive for pancytokeratin and negative for S-100, p63, c-KIT, androgen receptor, and neuroendocrine markers. Multiple foci of capsular or lymphovascular invasion were identified, but the Ki-67 labeling index was low (< 5%). Fluorescence in situ hybridization revealed concurrent alterations of MAML2 and EWSR1 gene. Further investigations with a larger number of cases with similar histological and molecular features will accurately classify this tumor.
Citations
Citations to this article as recorded by
Mesonephric-like Adenocarcinoma of the Ovary: Clinicopathological and Molecular Characteristics Hyun Hee Koh, Eunhyang Park, Hyun-Soo Kim Diagnostics.2022; 12(2): 326. CrossRef
The evolving role of molecular pathology in the diagnosis of salivary gland tumours with potential pitfalls Kanwalpreet Kaur, Shailee Mehta, Sangita Vanik, Priti Trivedi, Nirmalya Banerjee, Harsh Dhar, Sourav Datta, Subhadeep Karanjai European Archives of Oto-Rhino-Laryngology.2022; 279(8): 3769. CrossRef
Alveolar Soft Part Sarcoma of the Uterus: Clinicopathological and Molecular Characteristics Yurimi Lee, Kiyong Na, Ha Young Woo, Hyun-Soo Kim Diagnostics.2022; 12(5): 1102. CrossRef
Endometrioid Carcinomas of the Ovaries and Endometrium Involving Endocervical Polyps: Comprehensive Clinicopathological Analyses Jihee Sohn, Yurimi Lee, Hyun-Soo Kim Diagnostics.2022; 12(10): 2339. CrossRef
Mesonephric-like Differentiation of Endometrial Endometrioid Carcinoma: Clinicopathological and Molecular Characteristics Distinct from Those of Uterine Mesonephric-like Adenocarcinoma Sujin Park, Go Eun Bae, Jiyoung Kim, Hyun-Soo Kim Diagnostics.2021; 11(8): 1450. CrossRef
Mesonephric-like Adenocarcinoma of the Uterine Corpus: Comprehensive Immunohistochemical Analyses Using Markers for Mesonephric, Endometrioid and Serous Tumors Hyunjin Kim, Kiyong Na, Go Eun Bae, Hyun-Soo Kim Diagnostics.2021; 11(11): 2042. CrossRef
Rare cases of lung adenocarcinoma (LUAD) with concomitant epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) translocation have been reported. However, their clonal and evolutional relationship remains unclear. We report a case of early-stage EGFR-mutated LUAD with a focal concomitant EGFR/ALK alteration. A 63-year-old male underwent lobectomy to remove a 1.9-cm-sized lung nodule, which was diagnosed with EGFR-mutated LUAD. ALK immunohistochemistry (IHC) showed focal positivity within the part of the tumor characterized by lepidic pattern, also confirmed by fluorescence in-situ hybridization (FISH). Targeted next-generation sequencing was performed separately on the ALK IHC/FISH-positive and -negative areas. EGFR L833V/L858R mutations were detected in both areas, whereas EML4 (echinoderm microtubule-associated protein-like 4)-ALK translocations was confirmed only in the ALK IHC/FISH-positive area, suggesting the divergence of an EGFR/ALK co-altered subclone from the original EGFR-mutant clone. Our study suggests that concurrent alterations of EGFR and ALK can arise via divergent tumor evolution, even in the relatively early phases of tumorigenesis.
A 57-year-old man with left flank pain was referred to our institute. Computed tomography scans revealed two enhancing masses in the left kidney. The clinical diagnosis was renal cell carcinoma (RCC). He underwent a radical nephrectomy with an adrenalectomy. Two well-circumscribed solid masses in the hilum and the lower pole (4.5 × 3.5 cm and 7.0 × 4.1 cm) were present. Poorly cohesive uniform round to polygonal epithelioid cells making solid sheets accounted for most of the tumor area. The initial diagnosis was RCC, undifferentiated with rhabdoid features. As the tumor showed loss of INI1 expression and a mutation in the SMARCB1 gene on chromosome 22, the revised diagnosis was a malignant rhabdoid tumor (MRT) of the kidney. To date, only a few cases of renal MRT in adults have been reported. To the best of our knowledge, this is the first report of MRT in the native kidney of an adult demonstrating a SMARCB1 gene mutation, a hallmark of MRT.
Hepatocellular adenoma: what we know, what we do not know, and why it matters Paulette Bioulac‐Sage, Annette S H Gouw, Charles Balabaud, Christine Sempoux Histopathology.2022; 80(6): 878. CrossRef
Hepatocellular adenomas: recent updates Haeryoung Kim, Young Nyun Park Journal of Pathology and Translational Medicine.2021; 55(3): 171. CrossRef
Use of 18F-FDG PET CT for Evaluation of Rarely Seen Adenocarcinoma of Cervix Uteri Before and After Therapy Esra Arslan, Özge Vural Topuz, Meftune Özhan, Özgül Ekmekçioğlu, Mehmet Deniz Altıparmak, Kerim Sönmezoğlu Indian Journal of Gynecologic Oncology.2021;[Epub] CrossRef