Diagn Pathol [JOURNAL]
Sun
200 papers
Pathology of peripheral neuroblastic tumors.
Conces MR, Shibui Y, Shimada H
Diagn Pathol · 2026 Jan · PMID 41612478 · Full text
Neuroblastoma is the most prevalent extracranial solid tumor in pediatric age populations worldwide and the most common neoplastic disease diagnosed in the first year of life. The term neuroblastoma often encompasses all...
Neuroblastoma is the most prevalent extracranial solid tumor in pediatric age populations worldwide and the most common neoplastic disease diagnosed in the first year of life. The term neuroblastoma often encompasses all peripheral neuroblastic tumors (pNTs including neuroblastoma, ganglioneuroblastoma, and ganglioneuroma) of neural crest origin. Since pNTs demonstrate a wide range of clinical behaviors, including spontaneous regression, tumor differentiation/maturation, and aggressive progression refractory to even intensive treatment modalities, these tumors are believed to be distinguished into different biological/molecular groups. For the practical purpose, risk classification systems have been developed based on combinations of so-called prognostic factors.In this review of pNTs, we describe a history of pathology, summarize epidemiology and clinical features, and outline International Neuroblastoma Pathology Classification (INPC). Then we discuss advantages and limitations of core needle biopsy and conventional biopsy of neuroblastoma. Besides the INPC, we also describe other prognostic factors, such as age at diagnosis, clinical stage, and molecular/genetic factors, since they are included in widely used Risk Classification Systems. Additionally, we discuss further molecular abnormalities closely associated with highly aggressive neruoblastomas. Towards the end, we touch on rapidly advancing technologies for establishing an artificial intelligence-assisted INPC system.
Pediatric malignant testicular germ cell tumors: a developmental and comparative perspective.
Chen S, Matoso A
Diagn Pathol · 2026 Jan · PMID 41593694 · Full text
Malignant testicular germ cell tumors exhibit significant histologic diversity, particularly across pediatric age groups. Prepubertal patients more commonly develop yolk sac tumors, whereas postpubertal adolescents are m...
Malignant testicular germ cell tumors exhibit significant histologic diversity, particularly across pediatric age groups. Prepubertal patients more commonly develop yolk sac tumors, whereas postpubertal adolescents are more likely to present with mixed germ cell tumors arising from germ cell neoplasia in situ. Although clinical presentations may vary, histologic evaluation and immunohistochemistry remain the cornerstone of diagnosis. Additionally, molecular findings-especially the presence of isochromosome 12p-play a crucial role in prognosis. This review underscores the developmental origins and heterogeneity of malignant testicular germ cell tumors in pediatric populations and provides some contrast with their development in adults.
Pulmonary metastasis of nasal cavity DEK::AFF2 squamous cell carcinoma: case report and diagnostic insights.
Chen Y, Lu M, Sun Z … +4 more , Liu K, Meng J, Yan H, Chang B
Diagn Pathol · 2026 Jan · PMID 41588521 · Full text
DEK::AFF2 fusion carcinoma is an emerging sinonasal tract non-keratinizing squamous cell carcinoma (SCC) variant, characterized by deceptively bland morphology, frequent local recurrence, and metastasis in a subset of ca...
DEK::AFF2 fusion carcinoma is an emerging sinonasal tract non-keratinizing squamous cell carcinoma (SCC) variant, characterized by deceptively bland morphology, frequent local recurrence, and metastasis in a subset of cases. Owing to its histologic mimicry, misdiagnosis remains common. We report a case of DEK::AFF2 neoplasm exhibiting malignant histological evidence strictly confined to the pulmonary “metastatic” lesion despite persistent benign radiologic and pathologic features in six nasal cavity tumor resections over two decades in a 35-year-old male. The patient was initially diagnosed with inverted papilloma (IP) of the nasal cavity. Histopathologic reassessment of the lung lesions, however, demonstrated divergent morphology—hybrid SCC and IP-like components. Molecular studies (FISH, RNA-seq) confirmed identical DEK::AFF2 fusion in both nasal cavity and pulmonary tumors, supporting clonal spread. This case underscores that DEK::AFF2 sinonasal carcinomas can retain benign histology in primary and recurrent lesions while exhibiting overt malignancy in “metastatic” sites. For sinonasal papillomatous tumors, even if the primary tumor lacks overt malignant histological features, atypical clinical behaviors, such as persistent recurrence or development of distant similar lesions, should raise suspicion for DEK::AFF2 SCC. DEK FISH or RNA sequencing should be considered for definitive diagnosis when clinically indicated.
TTF-1, CDX-2, PAX-8 and GATA-3 immunoexpression in a large serie of extrapulmonary small cell neuroendocrine carcinomas: a study of 138 cases.
Pavlíčková K, Waldauf P, Dundr P … +10 more , Švajdler M, Fabian P, Zambo IS, Flídrová M, Laco J, Hornychová H, Delongová P, Škarda J, Hrudka J, Matěj R
Diagn Pathol · 2026 Jan · PMID 41588454 · Full text
BACKGROUND: Extrapulmonary small cell neuroendocrine carcinoma (EP-SC) is a rare malignancy with a poor prognosis. In our study, one hundred and thirty-eight EP-SCNC tissue samples underwent a complex analysis. METHOD: M...
BACKGROUND: Extrapulmonary small cell neuroendocrine carcinoma (EP-SC) is a rare malignancy with a poor prognosis. In our study, one hundred and thirty-eight EP-SCNC tissue samples underwent a complex analysis. METHOD: Multicentric study included 138 high-grade small cell carcinomas exhibiting neuroendocrine morphology without known pulmonary involvement. Using TMA, we studied the possible benefit of TTF-1 (DAKO, clone 8G7G3/1, dilution 1:200), CDX-2 (DAKO, ready to use kit DAK-CDX2), PAX-8 (Cell Marque, polyclonal, dilution 1:50) and GATA-3 (Cell Marque, clone L50-823, 1:200) immunohistochemical analyses for determining the primary site of EP-SCNC origin. For statistical analyses, the Kaplan-Meier, the Cox regressions analyses, the Pearson chi-square test and the Fisher’s exact test were used. RESULTS: The median survival of our cohort was 11.5 months. Patients younger than 70 years had significantly better overall survival (p = 0.024). Across the full cohort, CDX-2 positivity was found in 19 tumors (13.9%), TTF-1 in 35 tumors (25.7%), PAX-8 in 63 tumors (46.3%) and GATA-3 in 8 tumors (6.5%), regardless of tumor origin. The expression of CDX-2, PAX-8 and GATA-3 did not differ significantly among different organ systems (p = 0.2; 0.3 and 0.12), respectively. The expression of TTF-1 differed significantly in tumors from various sites of origin (p = 0.009), expressed more often in breast, pancreatic, and genitourinary tumors. Interestingly, TTF-1 expression proved to have a negative prognostic impact relative to patient survival (age-adjusted Cox regression analysis, HR = 1.62, 95%CI:1.06–2.47, p = 0.021). CONCLUSION: As most patients with EP-SCNC had a metastatic presentation, finding the primary tumor origin, which is important for patient prognoses, is both challenging and important at the same time. Only TTF-1 immunohistochemical analysis proved to be helpful with this task. Moreover, a diagnosis of primary lung small cell carcinoma cannot be established based on TTF-1 positivity, since only 25.7% of EP-SCNC in our study displayed TTF-1 positivity.
A novel immunohistochemical staining method of frozen sections improves the intraoperative diagnosis of Sclerosing Pneumocytoma and bronchiolar adenoma.
Liu Q, Luo J, Liang Q
Diagn Pathol · 2026 Jan · PMID 41588376 · Full text
BACKGROUND: Sclerosing Pneumocytoma (SP) and Bronchial Adenoma (BA) are rare benign tumors that are morphologically difficult to differentiate from lung adenocarcinoma during intraoperative diagnosis. Effective IHC on fr...
BACKGROUND: Sclerosing Pneumocytoma (SP) and Bronchial Adenoma (BA) are rare benign tumors that are morphologically difficult to differentiate from lung adenocarcinoma during intraoperative diagnosis. Effective IHC on frozen section might be beneficial for their recognition. This study introduced a novel IHC method that could be applied to intraoperative frozen sections. Its performance was well demonstrated, and the improvement in pathological diagnosis and surgical decisions was analyzed. METHODS: Comparative cohorts of SP and BA were established from surgical samples. The influence of the novel method was analyzed using self-controlled samples. The diagnostic efficacy of the novel IHC on frozen sections was tested using selected markers. The impact of IHC using frozen sections on the pathological evaluations and surgical operations was analyzed. RESULTS: The new IHC protocol on frozen sections demonstrated superior performance. Compared to IHC on FFPE, the overall accuracy of the selected markers was satisfactory. It improved the diagnostic accuracy of junior pathologists, with the correct diagnosis rate increasing from 38.7% to 93.6% in SP and from 49.1% to 94.5% in BA. Additionally, the rate of lobectomy and segmentectomy decreased from 54.2% to 38.7% in the SP cohort. A unique group featuring single-layered bronchiolar adenomatoid lesions was described. CONCLUSIONS: The optimized IHC protocol for frozen sections enhances intraoperative diagnostic accuracy, facilitating improved surgical decision-making for SP and BA, thereby enhancing the management of diseases that require accurate intraoperative diagnosis. The clinical application of the new IHC method and the special group of adenomatoid lesions warrant further investigations.
Clinical and molecular characteristics of constitutional mismatch repair deficiency syndrome: a case series of five children and appraisal of diagnostic guidelines.
Vazzano Goldstone J, Logan SJ, Wilkins BJ … +10 more , MacFarland SP, Conces M, Boué DR, Pierson CR, Kahwash S, Schieffer KM, Cottrell CE, Colace S, Zajo K, Shenoy A
Diagn Pathol · 2026 Jan · PMID 41572278 · Full text
DNA mismatch repair (MMR) is critical for maintaining genome integrity through correction of single-base mismatches and insertion-deletion loops arising from DNA replication. Heterozygous germline alteration of MMR genes...
DNA mismatch repair (MMR) is critical for maintaining genome integrity through correction of single-base mismatches and insertion-deletion loops arising from DNA replication. Heterozygous germline alteration of MMR genes (MSH2, MSH6, MLH1, PMS2) cause autosomal dominant Lynch syndrome (LS), most commonly manifesting as colonic or endometrial cancers, although brain, ovarian, and other organ systems may be involved. Neoplasia in LS usually arises after the age of 30 years. Constitutional mismatch repair deficiency (CMMRD) is inherited in an autosomal recessive manner due to biallelic germline alteration in one of the four MMR genes. Individuals with CMMRD typically develop cancer in the first decade of life, although some may present during the second decade. We present a series of five children who developed cancer prior to the age of 20 years (range: 2-12 years) with malignancies including colonic adenocarcinoma (N = 1), T-lymphoblastic lymphoma (N = 3), and high-grade glioma (N = 4). Two patients with MSH6 alterations developed a constellation of three primary tumors: high-grade glioma, T-lymphoblastic lymphoma, and colonic neoplasia including colonic adenocarcinoma in one patient and a tubular adenoma in the other.
Histological features of liver biopsy in patients with COVID-19: a single institution experience with long term follow-up outcome.
Chi Z, Moghal N, Rakheja D … +1 more , Peng L
Diagn Pathol · 2026 Jan · PMID 41566463 · Full text
BACKGROUND: COVID-19 is caused by SARS-CoV2, which primarily produces respiratory disease. Although liver enzyme abnormalities are common in patients with COVID-19, little is known about histological changes in the liver...
BACKGROUND: COVID-19 is caused by SARS-CoV2, which primarily produces respiratory disease. Although liver enzyme abnormalities are common in patients with COVID-19, little is known about histological changes in the liver. Most of the available information is based on autopsy studies, with limited liver biopsy studies in living patients. METHODS: Liver biopsies performed between March 2021 and September 2021 in patients with a history of COVID-19 were retrieved, and 17 biopsies were reviewed. Additionally, immunohistochemical staining for the SARS-CoV2 nucleocapsid protein was performed in all cases. The clinical follow-up period was 36 months. RESULTS: After reviewing the clinical data, the biopsies were grouped into three cohorts: (1) those with no underlying liver disease, (2) those with preexisting liver disease, and (3) those with liver post-transplant allografts. In patients without underlying liver disease, there were small clusters of debris-laden macrophages in the portal areas and lobules, as highlighted by periodic acid-Schiff and diastase staining. Increased mitosis and binucleated hepatocytes were common, and rare micro-abscesses were also observed. These findings indicated mild non-specific hepatitis, and no severe inflammatory infiltrates were observed in portal areas or lobules. These features are highly suggestive of hepatitis resolution. Patients with previous liver disease showed microscopic features compatible with underlying liver disease, without any additional features that could be attributed to COVID-19. Posttransplant allograft biopsies showed no special features that could be described as occurring solely due to COVID-19. All patients tested negative on SARS-CoV2 nucleoprotein immunostains. CONCLUSIONS: Liver biopsies performed after COVID-19 demonstrated a mildly resolved hepatitis-like pattern. 36 months after biopsy, all patients in Group 1 and all surviving patients in Group 2 and 3 presented normal liver enzyme levels. It is therefore, from this small case series, that the liver may not be the target of significant inflammatory damage in COVID-19 and that liver injuries are resolved over time.
Benign prostatic hyperplasia to HPIN to carcinoma; the impact of mast cells and VEGF.
Sivrikoz ON, Eroğlu A, Öztürk B … +2 more , Öztop İ, Sanal SM
Diagn Pathol · 2026 Jan · PMID 41559778 · Full text
BACKGROUND: The process of transformation from Benign Prostatic Hyperplasia (BPH) to Prostate Cancer (PCa) is highly debatable; however, there is convincing information that it takes place in the background of inflammati...
BACKGROUND: The process of transformation from Benign Prostatic Hyperplasia (BPH) to Prostate Cancer (PCa) is highly debatable; however, there is convincing information that it takes place in the background of inflammation. Multifocal high-grade prostatic intraepithelial neoplasia (HPIN), intraductal carcinoma (IDC-P), atypical intraductal proliferation (AIP), atypical adenomatous hyperplasia (AAH)/ adenosis, and proliferative inflammatory atrophy (PIA) are considered as precursor lesions during such transformation by Working Group 1 at the ISUP Cancer Precursors Meeting in September 2024. We specifically emphasize the need for further investigation of the inflammatory process, where stromal epithelial activity, angiogenesis, and mast cells are involved. In this study, we investigated the role of vascular endothelial growth factor (VEGF), and MCs during its progression from BPH to PCa. Additionally, we investigated the relationship between MCs and Gleason Grade Group (GG), as well as other prognostic variables. METHODS: Retrospectively, 100 PCa patients whose pathology included areas of BPH and multifocal HPIN close to cancerous tissue. All the specimens were stained with CD117 as an MC marker and VEGF to evaluate for angiogenesis. RESULTS: While there was overall intense MC infiltration in all areas of BPH in general, it was relatively less intense in areas of carcinomatous tissue. Nevertheless, MC infiltration intensified with higher GG. Similarly, with increasing MC infiltration in cancerous and HPIN tissues, VEGF staining also intensified, specifically in glandular areas. In HPIN areas, the relationship between MCs and VEGF was intermediate between BPH and cancerous areas, representing a progression. CONCLUSION: Stromal changes, stromal-epithelial interactions, and coexisting inflammatory changes are important elements in the development of BPH and PCa. We specifically investigated the intratumoral MC population and glandular VEGF staining intensity with increasing GG; thus, assessing the role of MCs and VEGF in tumor progression towards cancer development. MCs and VEGF staining characteristics in HPIN areas emphasize the efficient role these elements play in the transition of tissues from BPH to HPIN and eventually to PCa.
Sinonasal renal cell-like adenocarcinoma: a case report and literature review.
Chen L, Ding W, Xu P … +2 more , Li H, Zheng Y
Diagn Pathol · 2026 Jan · PMID 41559704 · Full text
OBJECTIVE: Sinonasal renal cell-like adenocarcinoma (SNRCLA) is a rare sinonasal carcinoma that is easily misdiagnosed. We aimed to reveal clinical clinicopathological features, molecular genetic characteristics, treatme...
OBJECTIVE: Sinonasal renal cell-like adenocarcinoma (SNRCLA) is a rare sinonasal carcinoma that is easily misdiagnosed. We aimed to reveal clinical clinicopathological features, molecular genetic characteristics, treatment and prognosis of SNRCLA. METHODS : The pathological diagnosis and differential diagnosis of a case of SNRCLA and the literature was reviewed. RESULTS: Immunohistochemical analysis demonstrated positive expression of cytokeratin (CK)7, Sox-10, and carbonic anhydrase (CA)-IX, while negative expression was observed for CK20, CDX-2, Villin, Thyroid transcription factor(TTF)-1, Dog-1, Epstein–Barr virus viral capsid antigen (EBV-VCA), CD10,Renal cell carcinoma marker(RCC Ma), paired box(PAX)8, calponin, p63,and S-100. The positive proportion of Ki67 is less than 5%, and periodic acid-Schiff (PAS) staining confirmed glycogen content in the tumor cells. Epidermal growth factor receptor (EGFR) protein was overexpressed, but the EGFR gene was not mutated. The ETV6 gene was analyzed using fluorescence in situ hybridization (FISH) technology, but no rearrangement was detected. These mutations were detected using next-generation sequencing (NGS), including BRAF NM_004333:exon11 c.1357 C > G p.P453A, NM_000314:exon1 c.70_75del p.D24_L25del, MTOR NM_004958:exon39 c.5417 A > G p.H1806R, and PIK3CA NM_006218:exon5 c.1031T > G p.V344G. Following surgery and radiotherapy, no clinical or radiological evidence of recurrence or metastasis was observed during a follow-up period of 76 months. CONCLUSION: It is beneficial for diagnosis of SRCLC that clinical history, morphological characteristics and immunohistochemistry are combined. It is an indolent tumor, the potential for local recurrence requires individualized management and post-treatment surveillance. Meanwhile, It warrants further examination in molecular genetic characteristics.
ESM1 and protein lysine L-lactylation modification (Pan-kla) in ovarian cancer: coexpression, clinical significance, and prognostic value.
Zhou W, Zhou Y, Zeng T … +4 more , Gao Z, Deng Y, Li Y, Quan X
Diagn Pathol · 2026 Jan · PMID 41555342 · Full text
BACKGROUND: Ovarian cancer (OC) remains a highly lethal gynaecologic malignancy. Endothelial cell-specific molecule 1 (ESM1) and protein lysine L-lactylation modification (Pan-kla) are key players in tumour microenvironm...
BACKGROUND: Ovarian cancer (OC) remains a highly lethal gynaecologic malignancy. Endothelial cell-specific molecule 1 (ESM1) and protein lysine L-lactylation modification (Pan-kla) are key players in tumour microenvironment regulation, which involves metabolic reprogramming, angiogenesis, and immune modulation. However, their coexpression patterns, clinical relevance, and synergistic prognostic impact in OC patients have not been fully elucidated. METHODS: In this study, immunohistochemistry (IHC) was used to analyse ESM1 and Pan-kla expression in 131 ovarian cancer tissue samples from patients diagnosed between 2014 and 2024. Clinical parameters (e.g., FIGO stage, CA125 level, and ascites) and survival data were collected. Statistical analyses, including Kaplan–Meier survival and risk stratification, were performed using R software. RESULTS: ESM1 and Pan-kla were significantly overexpressed in OC tissues, with a strong positive correlation (P < 0.0001). High expression of both biomarkers was associated with adverse clinical features: advanced FIGO stage, elevated CA125 levels, and malignant ascites. Survival analysis revealed that high ESM1 expression increased the risk of death, whereas high Pan-kla expression increased the risk. Patients exhibiting combined ESM1/Pan-kla expression were stratified into four prognostic subgroups, with the dual-high group exhibiting the worst survival (P < 0.001). CONCLUSION: ESM1 and Pan-kla synergistically promote OC progression through metabolic–epigenetic cross-regulatory mechanisms. Their combined assessment provides robust prognostic stratification and reveals potential targets for overcoming therapeutic resistance in ovarian cancer.
Immunohistochemical expression of CANT1 and B3GNT3 in invasive ductal carcinoma of the breast: diagnostic and prognostic significance in lymph node metastasis.
Thabet DM, Abu Bakr ASWK
Diagn Pathol · 2026 Jan · PMID 41540462 · Full text
BACKGROUND: Breast cancer is a leading global health concern, with lymph node metastasis (LNM) being a key prognostic factor affecting patient outcomes. Glycosylation-related enzymes such as calcium-activated nucleotidas...
BACKGROUND: Breast cancer is a leading global health concern, with lymph node metastasis (LNM) being a key prognostic factor affecting patient outcomes. Glycosylation-related enzymes such as calcium-activated nucleotidase 1 (CANT1) and Beta-1,3-N-acetylglucosaminyltransferase 3 (B3GNT3) have been implicated in tumour progression, yet their roles in breast cancer, particularly invasive ductal carcinoma (IDC), are not well defined. This study investigates the immunohistochemical expression and correlation of CANT1 and B3GNT3 in IDC and their potential role in predicting LNM and clinical outcomes. MATERIALS AND METHODS: Slides from paraffin blocks of 140 IDC cases and 108 corresponding metastatic axillary lymph nodes were stained with CANT1 and B3GNT3 antibodies. Associations between markers' immunoreactivity and clinicopathological variables were evaluated. Progression-free survival (PFS) was analysed using the Kaplan-Meier method. The prognostic significance of each variable was evaluated using both univariate and multivariate Cox proportional hazards regression analyses. RESULTS: High CANT1 and B3GNT3 expression was observed in 47.1% and 45.7% of cases, respectively. Both markers were significantly associated with tumour grade, tumour stage, Nottingham prognostic index, lymph node status, lymph node ratio, Her2 status, Ki-67 proliferative index and distant metastasis. A significant positive correlation was found between CANT1 and B3GNT3 expression (p < 0.001). Co-expression of both markers was strongly associated with LNM, along with a significant difference in the expression levels of each marker between primary tumours and corresponding LNM. Univariate analysis showed that tumour grade, stage, ER status and high B3GNT3 expression were all significantly associated with worse PFS. Multivariate Cox regression identified B3GNT3 expression, tumour grade and tumour stage as independent predictors of poor prognosis in IDC. High expression levels of CANT1 and B3GNT3 were associated with reduced PFS across all IDC cases (p = 0.035 and p = 0.001, respectively). CONCLUSIONS: High CANT1 and B3GNT3 expressions are associated with aggressive clinicopathological features in IDC and predict unfavourable outcomes. These markers may serve as potential prognostic indicators and independent predictors of LNM in IDC patients.
Expression and significance of IL-27 and IL-35 in orbital fat in patients with severe TAO.
Wang B, Xu Z, Zhao X … +2 more , Zhang L, Zhang H
Diagn Pathol · 2026 Jan · PMID 41491491 · Full text
To detect the expression of Interleukin-27 (IL-27) and Interleukin-35 (IL-35) in orbital fat in patients with severe TAO (thyroid-related eye disease) exophthalmos, and to investigate its potential role and significance...
To detect the expression of Interleukin-27 (IL-27) and Interleukin-35 (IL-35) in orbital fat in patients with severe TAO (thyroid-related eye disease) exophthalmos, and to investigate its potential role and significance in the development of TAO. A study group of 30 patients (30 eyes) who underwent orbital decompression with severe TAO exophthalmos in the Department of Ophthalmology, Provincial Hospital affiliated to Shandong First Medical University from January 2022 to December 2023, the expression of IL-27 and IL-35 of the orbital adipose tissue was detected by western-blot, and which in 30 patients (30 eyes) underwent orbital fracture surgery and plastic repair as control group. The contents of IL-27 and IL-35 were higher in severe TAO patients than in normal controls, and the difference was significant (P < 0.01). IL-27 and IL-35 are significantly increased in the orbital fat of TAO patients with severe protrusion, suggesting that these two cytokines play key roles in the regulation of orbital fat dysplasia and the inflammatory process of TAO, and their expression has certain clinical value in the evaluation of TAO disease.
Langerhans cell histiocytosis manifesting at birth: a neonatal case with BRAF V600E mutation.
Tang W, Wang P
Diagn Pathol · 2025 Dec · PMID 41462262 · Full text
BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare histiocytic disorder characterized by clonal proliferation of abnormal Langerhans cells. We report a case of neonatal LCH diagnosed shortly after birth, an except...
BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare histiocytic disorder characterized by clonal proliferation of abnormal Langerhans cells. We report a case of neonatal LCH diagnosed shortly after birth, an exceptionally early presentation in the neonatal period that is exceedingly rare. The BRAF V600E mutation was detected in this neonate. CASE PRESENTATION: We report a full-term male neonate delivered via forceps assistance. Within 24 hours of birth, a firm 1×1 cm subcutaneous nodule on the left medial thigh progressively enlarged and ulcerated. By postnatal day 19, a dark red non-blanchable papule appeared on the left sole and rapidly spread to postauricular, cervical, truncal, and palmar regions, developing multiple ulcerative lesions. Skin biopsy confirmed Langerhans cell histiocytosis (LCH), with immunohistochemistry demonstrating diagnostic markers CD1a(+), Langerin(+), and S-100(+). Molecular testing detected the BRAF V600E mutation. Based on the early onset of the disease, rapidly progressive multifocal ulcerative skin lesions, and the presence of a high-risk BRAF mutation suggesting potential systemic dissemination, we initiated induction chemotherapy with vincristine combined with prednisone. Following treatment, the skin lesions resolved completely. The child is now 30 months old. During follow-up, an episode of otitis media occurred, but no recurrence or systemic organ involvement has been observed since. CONCLUSION: In this neonate, the initial localized skin lesions suggested potential spontaneous resolution. However, subsequent detection of the poor-prognosis BRAF V600E mutation indicated risk of systemic dissemination, prompting initiation of combination chemotherapy. Skin lesions resolved completely following vinblastine/prednisone therapy. Otitis media (an extracutaneous manifestation) emerging during follow-up further validated the treatment necessity, with no recurrence or new systemic manifestations observed thereafter.
The diagnostic dilemma of idiopathic granulomatous mastitis with an emphasis on histopathologic findings.
Anousha K, Jahanbin B, Ardalan FA … +3 more , Soleimani V, Azizi M, Rezvani A
Diagn Pathol · 2025 Dec · PMID 41456021 · Full text
BACKGROUND: Idiopathic granulomatous mastitis (IGM) is a rare benign inflammatory breast condition with diverse clinical and radiologic features, often misdiagnosed as malignancy prior to sampling. Therefore, histologica...
BACKGROUND: Idiopathic granulomatous mastitis (IGM) is a rare benign inflammatory breast condition with diverse clinical and radiologic features, often misdiagnosed as malignancy prior to sampling. Therefore, histological findings are one of the most essential bases of diagnosis. METHODS: We retrospectively searched the histopathologic database of the Cancer Institute of Imam Hospital for IGM cases and collected clinical and radiological data. After ruling out other causes of granulomatous mastitis, the histopathologic features of each case were evaluated. The pattern of inflammation was classed as lobulocentric, lobular spared, or confluent. The presence of granulomas was evaluated based on descriptive features, including well-formed or poorly defined granulomas, as well as the presence or absence of multinucleated giant cells. Granulation tissue, empty space, fat necrosis, and necrosis were also assessed. RESULTS: Overall, 40 cases of IGM were reviewed. All patients were female, within the age range of 22 to 64, with the majority falling into the 30-39 category. The most common clinical manifestation was a palpable mass. 30% of patients had a history of breastfeeding over the past 5 years, and one patient had a history of prolactinoma. BI-RADS 4a was the most reported radiologic score. In histopathologic assessment, lobulocentric inflammation was reported as a predominant finding (45% of cases). Granuloma was present in 39 cases (97.5%), but was only well-defined in 33 cases (82.5%). Neutrophilic aggregates were present in 37 cases (92.5%). CONCLUSION: The diagnosis of IGM depends on assessing the clinical and radiologic findings along with pathologic features. IGM is microscopically defined by a non-caseating lobulocentric granulomatous inflammation, composed of tight aggregates of epithelioid histiocytes. One of the variants, cystic neutrophilic granulomatous mastitis (CNGM), is characterized by the presence of cystic empty vacuoles lined by neutrophils.
Tumor-infiltrating neutrophil is an independent prognostic factor in pancreatic ductal adenocarcinoma.
Son SM, Han HS, Lee HC … +2 more , Lee OJ, Woo CG
Diagn Pathol · 2025 Dec · PMID 41430709 · Full text
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies. Tumor-infiltrating neutrophils (TINs) have been implicated in tumor progression and poor prognosis; however, their roles in...
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies. Tumor-infiltrating neutrophils (TINs) have been implicated in tumor progression and poor prognosis; however, their roles in PDAC remain unclear. TINs have been shown to granulocytic myeloid-derived suppressor cells (G-MDSCs) which inhibit adaptive immune responses and share morphological and functional features with classical neutrophils. G-MDSCs, unlike classical neutrophils, express myeloperoxidase (MPO). We evaluated the significance of TINs and MPO expression as a marker for prognosis in the PDAC. METHODS: We retrospectively analyzed 128 patients with surgically resected PDAC. The presence of TIN was assessed on hematoxylin and eosin-stained slides and immunohistochemistry was performed for MPO. RESULTS: TINs were identified in 61.7% of patients with PDAC. Their presence was significantly associated with worse overall survival and recurrence-free survival. After adjusting for clinicopathological variables, TIN remained an independent predictor of a poor prognosis. MPO was expressed in all TIN within PDAC, but was absent in neutrophils within benign inflammatory conditions. CONCLUSIONS: TIN in PDAC represents an independent adverse prognostic factor and is likely to be G-MDSCs based on MPO expression. Assessing TIN and MPO status in preoperative biopsy specimens may offer valuable prognostic information and guide future therapeutic strategies for PDAC.
Application value of TPAS staining technique for cervical exfoliated cells in cervical cancer screening.
Chen G, Zhang W, HuYan Y … +4 more , Yang Y, Li W, Feng G, Lu Z
Diagn Pathol · 2025 Dec · PMID 41430333 · Full text
BACKGROUND: Recent studies have shown that tumor cell membranes exhibit lower polarity than normal cell membranes, a characteristic that can be harnessed for cancer diagnosis. TPAS (viscosity-responsive plasma membrane p...
BACKGROUND: Recent studies have shown that tumor cell membranes exhibit lower polarity than normal cell membranes, a characteristic that can be harnessed for cancer diagnosis. TPAS (viscosity-responsive plasma membrane probe), a recently developed staining method using cell membrane polarity probes, may selectively visualize cervical cancer cells by targeting membrane polarity differences, offering a potential new approach for cervical cancer screening.To investigate the diagnostic value of TPAS staining combined with liquid-based thin-layer cytological testing (TCT) and human papillomavirus (HPV) testing in detecting cervical cancer. METHODS: A total of 100 patients with suspected cervical precancerous lesions from the People's Hospital of Shaanxi Province between May 2024 and May 2025 were studied. All patients underwent TPAS testing, HPV testing and TCT. Biopsy results were the gold standard for evaluating positivity rates and diagnostic values of the tests, both individually and in combination. RESULTS: Among the 100 participants, the positive rates of the tests were as follows: TPAS detection rate was 86.7%, HPV detection rate was 80%, TCT rate 66.7%, and TCT + HPV rate was 35.00%. The combined TPAS + HPV testing showed higher accuracy (72.00%) and sensitivity(70.6%) than TCT + HPV (58.0%)and (54.1%), and the differences were statistically significant ((χ2 = 14.00,P = 0.0002). CONCLUSION: TPAS combined with HPV testing has high specificity, sensitivity and accuracy, making it a promising approach for cervical cancer diagnosis.
Assessment of histopathology and cytology request form documentation quality using six Sigma and Pareto analysis in Benghazi, Libya.
Hamid H, Naas H, Alshaqabi MA … +6 more , Gebril MF, Gheryani NA, Alhabone AA, Ahmida MHS, Elmansoury AM, Najah M
Diagn Pathol · 2025 Dec · PMID 41408304 · Full text
BACKGROUND: Histopathology and cytology request forms are pivotal in the pre-analytical phase of laboratory testing, where incomplete or erroneous documentation on these forms can compromise the entire testing process. T...
BACKGROUND: Histopathology and cytology request forms are pivotal in the pre-analytical phase of laboratory testing, where incomplete or erroneous documentation on these forms can compromise the entire testing process. This study aimed to assess the documentation quality and process performance of histopathology and cytology request forms using Six Sigma and Pareto analysis in three private laboratories in Benghazi, Libya. METHODS: A retrospective cross-sectional study was conducted on 1,181 request forms collected from February to April 2025. A structured checklist encompassing five documentation domains and 15 quality indicators based on WHO guidelines was used to assess form completeness. Six Sigma metrics including Defects per Unit (DPU), Defects per Million Opportunities (DPMO), Sigma level, and Yield (%), along with Pareto analysis, were applied to evaluate and prioritize quality deficiencies. RESULTS: None of the evaluated request forms achieved full compliance with documentation standards. The overall process performance was unacceptable, with a Sigma level of 1.707 and a yield of 58.22%. Pareto analysis revealed that approximately 80% of documentation errors originated from three key domains: requesting clinician details, personal information, and clinical information. The requesting clinician details domain was the most deficient, with a Sigma level of 1.438 and a yield of 47.5%. The personal information domain followed, with a Sigma level of 1.867 and a yield of 64.31%. The clinical information domain showed a Sigma level of 1.263 and a yield of 40.6%. In contrast, the specimen details domain exhibited relatively better performance, with a Sigma level of 2.574 and a yield of 85.86%. CONCLUSIONS: Six Sigma and Pareto analysis were applied to identify critical deficiencies in documentation practices during the pre-analytical phase of histopathology services in Libya. The results highlight an urgent need to implement standardized staff training protocols, redesign request forms with mandatory fields, enforce accountability mechanisms, and establish robust quality monitoring systems. Low-cost tools-such as Excel-based compliance trackers and manual logbooks-can serve as effective interim solutions to enhance documentation compliance and support continuous quality improvement in resource-limited settings.
Low CDX2 expression and its clinicopathological associations in colorectal adenocarcinoma: prognostic insights from a retrospective cross-sectional study in Vietnam.
Minh Le H, Ho Ngoc Le T, Thi Tuyet Ngo H … +4 more , Thi Thu Luu T, Quoc Pham T, Huong Tran G, Thanh Ly T
Diagn Pathol · 2025 Dec · PMID 41388313 · Full text
BACKGROUND: CDX2, an intestine-specific transcription factor, is essential for colorectal epithelial differentiation and has been widely studied as a biomarker in colorectal adenocarcinoma (CRC). However, most previous s...
BACKGROUND: CDX2, an intestine-specific transcription factor, is essential for colorectal epithelial differentiation and has been widely studied as a biomarker in colorectal adenocarcinoma (CRC). However, most previous studies applied a binary evaluation (positive/negative), which may underestimate its clinical significance. METHODS: We conducted a retrospective cross-sectional study of 356 surgically resected CRC cases at the University Medical Center, Ho Chi Minh City. CDX2 expression was evaluated by immunohistochemistry using an immunoreactivity score (IRS) that combined staining ratio and intensity. Associations between CDX2 expression and clinicopathological features were analyzed using chi-square and logistic regression tests. RESULTS: High CDX2 expression was observed in 88.8% of tumors, whereas 11.2% showed low expression. Low CDX2 was significantly associated with poor histological differentiation (OR = 3.79; 95% CI: 1.11-12.93; p = 0.033) and advanced local stage pT4a-pT4b compared with pT1-pT3 (OR = 2.86; 95% CI: 1.47-5.58; p = 0.002). No significant associations were found with patient age or sex. The combined scoring system allowed clearer discrimination between biologically distinct subgroups than the traditional binary method. CONCLUSIONS: Low CDX2 expression is linked to aggressive pathological features and advanced tumor stage in CRC, highlighting its clinicopathological associations. Semi-quantitative evaluation of CDX2 using both staining ratio and intensity provides a more informative assessment that may aid risk stratification and guide clinical decision-making in CRC patients.
Concurrent seronegative spondyloarthropathy and Takayasu's arteritis: a case report and literature review.
Sun XH, Wu CY
Diagn Pathol · 2025 Dec · PMID 41372966 · Full text
Seronegative spondyloarthropathy (SpA) and Takayasu's arteritis (TA) are distinct chronic inflammatory conditions with autoimmune characteristics. While both conditions are relatively common, their concurrent occurrence...
Seronegative spondyloarthropathy (SpA) and Takayasu's arteritis (TA) are distinct chronic inflammatory conditions with autoimmune characteristics. While both conditions are relatively common, their concurrent occurrence is rare. This case report presents an individual diagnosed with both SpA and TA, detailing the clinical presentation, disease course, and therapeutic interventions. A review of relevant literature is also included to enhance clinical awareness of this uncommon combination. For that patients with SpA who exhibit elevated inflammatory markers, intermittent low-grade fever, fatigue, or inadequate response to standard therapies, it's better to undergo evaluation for the potential presence of TA. Early identification of TA in such cases may help mitigate the risks of misdiagnosis or delayed diagnosis.
Integrative prognostic model incorporating high mobility group box 1 subcellular localization and tumor-infiltrating lymphocytes in early-stage lung adenocarcinoma.
Liu Y, Shimasaki M, Kumagai M … +5 more , Han J, Shioya A, Sakurai M, Uramoto H, Yamada S
Diagn Pathol · 2025 Dec · PMID 41327377 · Full text
BACKGROUND: The prognostic impact of high mobility group box 1 (HMGB1) in lung adenocarcinoma may depend on its subcellular localization, while the density of tumor-infiltrating lymphocytes (TILs) reflects the host anti-...
BACKGROUND: The prognostic impact of high mobility group box 1 (HMGB1) in lung adenocarcinoma may depend on its subcellular localization, while the density of tumor-infiltrating lymphocytes (TILs) reflects the host anti-tumor immune response. However, the combined prognostic value of these two factors in early-stage lung adenocarcinoma remains unclear. METHODS: This retrospective study included 112 patients with pathological stage I-II lung adenocarcinoma who underwent complete surgical resection at our institution between 2007 and 2017. None received neoadjuvant chemotherapy or radiotherapy. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded tumor specimens to evaluate HMGB1 subcellular localization and stromal TILs infiltration. The latter was semi-quantitatively assessed according to the International TILs Working Group recommendations and dichotomized using the median value as the cutoff. Clinicopathological variables, including differentiation, pleural invasion, lymphovascular invasion, and pathological stage, were collected and correlated with HMGB1 localization and TIL status. Survival outcomes were analyzed using Kaplan-Meier and Cox proportional hazards models. Multivariable analyses were adjusted according to the events-per-variable (EPV) rules, and model diagnostics included proportional hazards testing and multicollinearity assessment. Interobserver agreement for HMGB1 localization was evaluated using Fleiss'κ statistics. RESULTS: Cytoplasmic HMGB1 expression and low TIL infiltration were significantly associated with adverse clinicopathological features, including poorer differentiation and higher rates of lymphovascular invasion. Both cytoplasmic HMGB1 and low TIL levels independently predicted a shorter DFS and OS. Patients with the combined phenotype of cytoplasmic HMGB1 and low TIL levels had the worst prognosis, with hazard ratios exceeding those of either factor alone. The integrative model based on HMGB1 localization and TIL status enhanced the prognostic discrimination beyond conventional clinicopathological parameters. CONCLUSIONS: HMGB1 subcellular localization and TIL infiltration are independent prognostic biomarkers of early-stage lung adenocarcinoma. An integrative model combining these parameters provides enhanced risk stratification and may inform individualized postoperative management strategies.
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