Background We report a new risk stratification of invasive stage papillary thyroid carcinomas (PTCs) by combining invasive status, using extrathyroid invasion (Ex) status, and tumor growth speed using the Ki-67 labeling index (LI). Methods: We examined tumor recurrence in 167 patients with PTC who were surgically treated at the Kindai University Nara Hospital between 2010 and 2022. The patients were classified according to the degree of invasion [negative (Ex0) or positive (Ex1, Ex2, and Ex3)] and tumor growth speed expressed with Ki-67 LI, as low (<5%) or high (>5%). This study confirmed previous findings that the disease-free survival (DFS) rate in PTCs significantly differed between patients with a high and low Ki-67 index. Results: When combining Ex status (negative or positive) and Ki-67 proliferation status (low or high), the DFS rate of invasion in the negative, low Ki-67 LI group was only 1.1%, while that of invasion in the positive, high Ki-67 LI was 44.1%. This study reports for the first time that recurrence risks can be stratified accurately when combining carcinoma’s essential two features of extrathyroid invasion status and tumor growth speed. Conclusions: We believe the evidence for low tumor recurrence risk may contribute to use of more conservative treatment options for invasive-stage PTCs and help alleviate patient anxiety about tumor recurrence and death.
Exposure to post-transplant liver biopsies varies among pathology residencies and largely depends on the institution's training program, particularly if the hospital has a liver transplant program. The interpretation of biopsies from transplanted livers presents its own set of challenges, even for those with a solid understanding of non-transplant medical liver biopsies. In this review, we aim to provide a succinct, step-by-step approach to help you interpret liver transplant biopsies. This article may be beneficial for residents interested in liver pathology, gastrointestinal and liver pathology fellows in the early stages of training, clinical gastroenterology and hepatology fellows, hepatologists and general pathologists who are curious about this niche.
Cervical cancer screening during pregnancy presents unique challenges for cytologic interpretation. This review focuses on pregnancy-associated cytomorphological changes and their impact on diagnosis of cervical intraepithelial neoplasia (CIN) and cervical cancer. Pregnancy-induced alterations include navicular cells, hyperplastic endocervical cells, immature metaplastic cells, and occasional decidual cells or trophoblasts. These changes can mimic abnormalities such as koilocytosis, adenocarcinoma in situ, and high-grade squamous intraepithelial lesions, potentially leading to misdiagnosis. Careful attention to nuclear features and awareness of pregnancy-related changes are crucial for correct interpretation. The natural history of CIN during pregnancy shows higher regression rates, particularly for CIN 2, with minimal risk of progression. Management of abnormal cytology follows modified risk-based guidelines to avoid invasive procedures, with treatment typically deferred until postpartum. The findings reported in this review emphasize the importance of considering pregnancy status in cytological interpretation, highlight potential problems, and provide guidance on differentiating benign pregnancy-related changes from true abnormalities. Understanding these nuances is essential for accurate diagnosis and proper management of cervical abnormalities in pregnant women.
Background Colorectal carcinomas (CRCs) with caudal-type homeobox 2 (CDX2) loss are recognized to pursue an aggressive behavior but tend to be accompanied by a high density of tumor-infiltrating lymphocytes (TILs). However, little is known about whether there is an interplay between CDX2 loss and TIL density in the survival of patients with CRC.
Methods Stage III CRC tissues were assessed for CDX2 loss using immunohistochemistry and analyzed for their densities of CD8 TILs in both intraepithelial (iTILs) and stromal areas using a machine learning-based analytic method.
Results CDX2 loss was significantly associated with a higher density of CD8 TILs in both intraepithelial and stromal areas. Both CDX2 loss and a high CD8 iTIL density were found to be prognostic parameters and showed hazard ratios of 2.314 (1.050–5.100) and 0.378 (0.175–0.817), respectively, for cancer-specific survival. A subset of CRCs with retained CDX2 expression and a high density of CD8 iTILs showed the best clinical outcome (hazard ratio of 0.138 [0.023–0.826]), whereas a subset with CDX2 loss and a high density of CD8 iTILs exhibited the worst clinical outcome (15.781 [3.939–63.230]).
Conclusions Altogether, a high density of CD8 iTILs did not make a difference in the survival of patients with CRC with CDX2 loss. The combination of CDX2 expression and intraepithelial CD8 TIL density was an independent prognostic marker in adjuvant chemotherapy-treated patients with stage III CRC.
Pancreatic neuroendocrine microtumor (PNEMT) is a neuroendocrine tumor (NET) < 0.5 cm in diameter, and it is considered benign. We report a PNEMT with high-grade transformation (HGT). A man in his 60s with von Hippel-Lindau syndrome underwent surgical resection of a NET. A second sub-centimeter nodule with a nodule-in-nodule pattern was discovered. The 0.4 cm outer nodule contained clear columnar cells with round nuclei and indistinct nucleoli, while the 0.1 cm inner nodule had eosinophilic cells with an increased nuclear to cytoplasmic ratio, vesicular nuclei, and prominent nucleoli. Tumor cells in the outer and inner nodules were synaptophysin and chromogranin positive. Only the inner nodule was p53 positive, while the outer nodule was exclusively positive for carbonic anhydrase 9 and vimentin. The Ki-67 labeling indices for the outer and inner nodules were 2.1% (grade 1) and 44.3% (grade 3), respectively. This nodule was determined to be a PNEMT with HGT. Our findings suggest that a PNEMT may not always be benign and can undergo HGT.
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Molecular Basis of Pancreatic Neuroendocrine Tumors Alesia Maluchenko, Denis Maksimov, Zoia Antysheva, Julia Krupinova, Ekaterina Avsievich, Olga Glazova, Natalia Bodunova, Nikolay Karnaukhov, Ilia Feidorov, Diana Salimgereeva, Mark Voloshin, Pavel Volchkov International Journal of Molecular Sciences.2024; 25(20): 11017. CrossRef
Background Follicular tumors include follicular thyroid adenomas and carcinomas; however, it is difficult to distinguish between the two when the cytology or biopsy material is obtained from a portion of the tumor. The presence or absence of invasion in the resected material is used to differentiate between adenomas and carcinomas, which often results in the unnecessary removal of the adenomas. If nodules that may be follicular thyroid carcinomas are identified preoperatively, active surveillance of other nodules as adenomas is possible, which reduces the risk of surgical complications and the expenses incurred during medical treatment. Therefore, we aimed to identify biomarkers in the invasive subpopulation of follicular tumor cells.
Methods We performed a spatial transcriptome analysis of a case of follicular thyroid carcinoma and examined the dynamics of CD74 expression in 36 cases.
Results We identified a subpopulation in a region close to the invasive area, and this subpopulation expressed high levels of CD74. Immunohistochemically, CD74 was highly expressed in the invasive and peripheral areas of the tumor.
Conclusions Although high CD74 expression has been reported in papillary and anaplastic thyroid carcinomas, it has not been analyzed in follicular thyroid carcinomas. Furthermore, the heterogeneity of CD74 expression in thyroid tumors has not yet been reported. The CD74-positive subpopulation identified in this study may be useful in predicting invasion of follicular thyroid carcinomas.
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Diagnosis of invasive encapsulated follicular variant papillary thyroid carcinoma by protein-based machine learning Truong Phan-Xuan Nguyen, Minh-Khang Le, Sittiruk Roytrakul, Shanop Shuangshoti, Nakarin Kitkumthorn, Somboon Keelawat Journal of Pathology and Translational Medicine.2025; 59(1): 39. CrossRef
Background The implication of the presence of tumor-infiltrating T lymphocytes (TIL-T) in diffuse large B-cell lymphoma (DLBCL) is yet to be elucidated. We aimed to investigate the effect of TIL-T levels on the prognosis of patients with DLBCL.
Methods Ninety-six patients with DLBCL were enrolled in the study. The TIL-T ratio was measured using QuPath, a digital pathology software package. The TIL-T ratio was investigated in three foci (highest, intermediate, and lowest) for each case, resulting in TIL-T–Max, TIL-T–Intermediate, and TIL-T–Min. The relationship between the TIL-T ratios and prognosis was investigated.
Results When 19% was used as the cutoff value for TIL-T–Max, 72 (75.0%) and 24 (25.0%) patients had high and low TIL-T–Max, respectively. A high TIL-T–Max was significantly associated with lower serum lactate dehydrogenase levels (p < .001), with patient group who achieved complete remission after RCHOP therapy (p < .001), and a low-risk revised International Prognostic Index score (p < .001). Univariate analysis showed that patients with a low TIL-T–Max had a significantly worse prognosis in overall survival compared to those with a high TIL-T–Max (p < .001); this difference remained significant in a multivariate analysis with Cox proportional hazards (hazard ratio, 7.55; 95% confidence interval, 2.54 to 22.42; p < .001).
Conclusions Patients with DLBCL with a high TIL-T–Max showed significantly better prognosis than those with a low TIL-T–Max, and the TIL-T–Max was an independent indicator of overall survival. These results suggest that evaluating TIL-T ratios using a digital pathology system is useful in predicting the prognosis of patients with DLBCL.
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Goblet cell adenocarcinoma (GCA) is a rare and distinctive amphicrine tumor comprised of goblet-like mucinous cells and neuroendocrine cells. It is believed to originate from pluripotent stem cells located at the base of crypts. GCA predominantly arises from the appendix, with a few reported cases in extra-appendiceal locations such as the colorectum, small intestine, and stomach. In this case report, we present a unique instance of a 64-year-old male who initially received a diagnosis of neuroendocrine carcinoma in the distal esophagus based on biopsy but, following resection, was subsequently re-diagnosed with GCA arising from Barrett’s esophagus.
Intravascular lymphoma is characterized by an exclusively intravascular distribution of tumor cells. Intravascular natural killer/T-cell lymphoma (IVNKTL) is extremely rare, highly aggressive, commonly Epstein-Barr virus (EBV)–positive, and predominantly affects the skin and central nervous system. Here we report a case of IVNKTL diagnosed in a 67-year-old female, presenting with persistent intermittent fever and skin rashes throughout the body. Incisional biopsy of an erythematous lesion on the chest exhibited aggregation of medium to large-sized atypical lymphoid cells confined to the lumen of small vessels that were positive for CD3, granzyme B, and CD56 on immunohistochemistry and EBV-encoded RNA in situ hybridization. EBV DNA was also detected in serum after diagnosis. With a review of 26 cases of IVNKTL to date, we suggest that active biopsy based on EBV DNA detection may facilitate early diagnosis of IVNKTL.
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J Pathol Transl Med. 2023;57(5):265-272. Published online September 15, 2023
Background The importance of molecular pathology tests has increased during the last decade, and there is a great need for efficient training of molecular pathology for pathology trainees and as continued medical education.
Methods The Molecular Pathology Study Group of the Korean Society of Pathologists appointed a task force composed of experienced molecular pathologists to develop a refined educational curriculum of molecular pathology. A 3-day online educational session was held based on the newly established structure of learning objectives; the audience were asked to score their understanding of 22 selected learning objectives before and after the session to assess the effect of structured education.
Results The structured objectives and goals of molecular pathology was established and posted as a web-based interface which can serve as a knowledge bank of molecular pathology. A total of 201 pathologists participated in the educational session. For all 22 learning objectives, the scores of self-reported understanding increased after educational session by 9.9 points on average (range, 6.6 to 17.0). The most effectively improved items were objectives from next-generation sequencing (NGS) section: ‘NGS library preparation and quality control’ (score increased from 51.8 to 68.8), ‘NGS interpretation of variants and reference database’ (score increased from 54.1 to 68.0), and ‘whole genome, whole exome, and targeted gene sequencing’ (score increased from 58.2 to 71.2). Qualitative responses regarding the adequacy of refined educational curriculum were collected, where favorable comments dominated.
Conclusions Approach toward the education of molecular pathology was refined, which would greatly benefit the future trainees.
Intrathyroidal metastasis of tonsillar squamous cell carcinoma is rare. To date, only six cases have been reported in the literature. This case was unusual and presented with thyromegaly before the diagnosis of the primary tumor. A 55-year-old male patient was suspected to have a primary thyroid tumor with nodal metastasis. The thyroid gland was diffusely enlarged, with no discernible mass. Histologically, the thyroid parenchyma revealed extensive endolymphatic tumor emboli, which were positive for p40 and p16 in a background of chronic lymphocytic thyroiditis. Positron emission tomography–computed tomography revealed hypermetabolic activity in the right tonsillar region. Tonsillar biopsy revealed human papillomavirus–positive squamous cell carcinoma. The present case is the first reported case of intrathyroidal metastasis of tonsillar squamous cell carcinoma with an initial clinical presentation of thyroid enlargement before the primary tumor of tonsillar cancer was diagnosed.
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The development and standardization of cytologic screening of the uterine cervix has dramatically decreased the prevalence of squamous cell carcinoma of the uterine cervix. Advances in the understanding of biology of human papillomavirus have contributed to upgrading the histologic diagnosis of the uterine cervix; however, cytologic screening that should triage those that need further management still poses several difficulties in interpretation. Cytologic features of high grade intraepithelial squamous lesion (HSIL) mimics including atrophy, immature metaplasia, and transitional metaplasia, and glandular lesion masquerades including tubal metaplasia and HSIL with glandular involvement are described with accentuation mainly on the differential points. When the cytologic features lie in a gray zone between the differentials, the most important key to the more accurate interpretation is sticking to the very basics of cytology; screening the background and cellular architecture, and then scrutinizing the nuclear and cytoplasmic details.
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Background The relationship between cystitis glandularis (CG) and bladder malignancy remains unclear.
Methods We identified the oncologic significance of CG at the molecular level using liquid chromatography-tandem mass spectrometry-based proteomic analysis of 10 CG, 12 urothelial carcinoma (UC), and nine normal urothelium (NU) specimens. Differentially expressed proteins (DEPs) were identified based on an analysis of variance false discovery rate < 0.05, and their functional enrichment was analyzed using a network model, Gene Set Enrichment Analysis, and Gene Ontology annotation.
Results We identified 9,890 proteins across all samples and 1,139 DEPs among the three entities. A substantial number of DEPs overlapped in CG/NU, distinct from UC. Interestingly, we found that a subset of DEP clusters (n = 53, 5%) was differentially expressed in NU but similarly between CG and UC. This “UC-like signature” was enriched for reactive oxygen species (ROS) and energy metabolism, growth and DNA repair, transport, motility, epithelial-mesenchymal transition, and cell survival. Using the top 10 shortlisted DEPs, including SOD2, PRKCD, CYCS, and HCLS1, we identified functional elements related to ROS metabolism, development, and transport using network analysis. The abundance of these four molecules in UC/CG than in NU was consistent with the oncologic functions in CG.
Conclusions Using a proteomic approach, we identified a predominantly non-neoplastic landscape of CG, which was closer to NU than to UC. We also confirmed a small subset of common DEPs in UC and CG, suggesting that altered ROS metabolism might imply potential cancerous risks in CG.
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