Intrahepatic cholangiocarcinoma (iCCA) is an aggressive primary liver malignancy with poor outcome. It is characterized by heterogeneous clinicopathological features as well as molecular landscapes. The updated World Health Organization (WHO) classification system underscores the critical distinction between small-duct and large-duct types, which exhibit distinct morphologic patterns, immunohistochemical profiles, molecular alterations, and clinical outcomes. Besides, rare and unique morphologic subtypes of iCCA continue to challenge diagnostic and treatment paradigms. This review provides an overview of the 2026 WHO classification and evolving concepts in iCCA, with a particular emphasis on the practical application of immunohistochemical and emerging molecular biomarkers essential for an accurate diagnosis and guiding targeted therapies. Furthermore, this manuscript addresses contemporary controversies and unresolved emerging practical issues with iCCA that are reshaping personalized therapeutic strategies and prognostication.
Vasculitis in the lung can be separated into infectious and non-infectious, and in systemic and localized ones. Three major categories in the lung are known, previously named Wegener’s granulomatosis, Churg-Strauss syndrome, and microscopic polyangiitis. The classification of vasculitis was proposed in 1994, including a size distribution for each type, an antinuclear and anticytoplasmic antibody profile (ANCA), and an organ location. In an updated classification (2011) the names for two of the most common primary vasculitis were replaced: Wegener`s granulomatosis by Granulomatosis with polyangiitis (GPA) and Churg-Strauss syndrome by Eosinophilic granulomatosis with polyangiitis (EGPA). This proposal has been critically discussed in meetings of the pulmonary working group of ESP (2025) and the Pulmonary Pathology Society Meeting (Quebec, 2026). There were doubts about the usefulness of the when applied in pulmonary pathology. A new proposal is presented here. This classification is based on pattern recognition, such as neutrophilic, eosinophilic, and other forms of vasculitis. As many other types of pulmonary vasculitis were not covered in the old nor in the new proposal, several variants are added. This applies for example to vasculitis seen in autoimmune diseases. There is no doubt, that a classification of vasculitis is important, to sort the type of vasculitis. If possible, such a classification should be useful not only in lung pathology but more general in any other organ system. However, in several organ systems the clinical picture and the laboratory test allow a diagnosis, which is not the case in lung. On CT scan most types of pulmonary vasculitis present with ground glass opacitis with/without nodules. Often biopsies are labelled as interstitial lung disease.
A 54-year-old male patient presented with a painful right cervical mass encasing the common carotid artery. Histologically, the tumor consisted of polygonal to spindle-shaped cells with mild nuclear atypia and low mitotic activity (0–1/10 high-power fields). No myxoid stroma or necrosis was identified, and desmin expression was patchy. GenMineTOP, a dual DNA-RNA comprehensive genomic profiling system, revealed a PML exon 7-JAK1 exon 5 fusion. The tumor was surgically unresectable because of circumferential encasement of the right common carotid artery. After radiotherapy followed by doxorubicin chemotherapy, no distant metastases developed during 17 months of follow-up. PML::JAK1 myofibroblastic sarcomas have previously been reported in four abdominal cases, most of which showed aggressive behavior. This cervical case broadens the anatomic spectrum of PML::JAK1 myofibroblastic sarcomas to include the head and neck region and further expands their morphologic spectrum.
Pleuroparenchymal fibroelastosis (PPFE) is a rare idiopathic interstitial lung disease; however, similar histopathological features are also observed in secondary PPFE (SPPFE) and in non-PPFE entities. This study aimed to distinguish idiopathic PPFE (IPPFE), SPPFE, and non-PPFE by quantitatively assessing elastic and collagen fibers using a deep learning–based approach. We analyzed 1728 Elastica van Gieson-stained slides obtained from 174 explanted lungs, including IPPFE (n = 14), SPPFE (n = 34), and non-PPFE (n = 126). Elastic and collagen fiber areas were quantified using DenseNet. Elastic fibers were classified into dense and faint types and assessed in upper and lower lobes. In the upper lobes, IPPFE showed a lower median collagen fiber area/fibrosis area ratio (0.480) than SPPFE (0.555, P = 0.0197) and non-PPFE (0.611, P < 0.0001), while SPPFE also showed a lower ratio than non-PPFE (P = 0.0063). IPPFE and SPPFE showed higher median dense elastic fiber area/fibrosis area ratios (0.117 and 0.097, respectively) than non-PPFE (0.041; P < 0.0001 for both). Likewise, IPPFE and SPPFE showed higher median faint elastic fiber area/fibrosis area ratios (0.385 and 0.342, respectively) than non-PPFE (0.295; P = 0.0001 and P < 0.0001, respectively). Similar trends were observed in the lower lobes, although differences in collagen fiber area/fibrosis area ratios were less pronounced. In conclusion, fibroelastosis in IPPFE is characterized by a uniform, dense elastic fiber framework with faint elastic fibers, whereas SPPFE shows heterogeneous fibroelastosis with mixed collagen fibers. These findings confirm that IPPFE is a distinct condition from SPPFE and non-PPFE.
Myxoid liposarcoma (MLPS) exhibits variable morphology and clinical behavior. Current grading systems, which rely on the proportion of round cell areas, were developed for resections, rather than core biopsies. Additionally, criteria for round cell and “transitional” areas are subjective/poorly reproducible. It has recently been suggested that nuclear grading may be superior to traditional grading in predicting the behavior of MLPS. We compared nuclear and cellularity-based grading in a large, multinational MLPS cohort. 280 MLPS (1990–2025) were reviewed; nuclear grade was assigned using a slight modification of the Kawaguchi et al. system. Disease‑specific survival (DSS), metastasis‑free survival (MFS), and disease‑free survival (DFS) were estimated and the performance of both grading systems was compared. Tumors occurred in 152 males/128 females (median 45 years of age; range 15–91 years) and predominantly involved proximal deep soft tissues. Initial diagnoses were made with needle core (149 cases) and open biopsies (131 cases). DDIT3 rearrangement was documented in 195 tumors. Nuclear grades were 1 (71 cases), 2 (121 cases) and 3 (88 cases); grades 1 and 2 were considered “low-grade” and grade 3 “high-grade”. Both systems assessed 192 (69
