Multinucleated giant cell pneumonia associated with heavy metals (GIP) is a rare disease of the pulmonary parenchyma, with just over one hundred cases reported in the scientific literature. It has been associated almost exclusively with occupational exposure to tungsten and cobalt. Although its pathogenesis is not fully understood, it has been proposed that exposure to an aetiological agent, together with an immune imbalance, underlies the pathophysiology of the characteristic microscopic findings, including fibrosis, multinucleated foreign-body giant cells and cannibalism. To date, iron has not been described as one of the causative agents. We present the case of a 41-year-old patient with documented occupational exposure to iron who developed respiratory failure. For the first time, findings consistent with GIP were demonstrated in the pulmonary parenchyma, with microscopic features that we consider specific.
Introduction: Odontogenic keratocyst (OKC) is a developmental odontogenic cyst that may occur sporadically (OKCsp) or in association with nevoid basal cell carcinoma syndrome (NBCCS) (OKC-sy). NBCCS is an autosomal dominant disorder characterised by morphological abnormalities and an increased predisposition to several neoplasms, including basal cell carcinomas. Mutations in the tumour suppressor gene PTCH1 have been reported in patients with OKC and NBCCS. PTCH1 participates in a signalling cascade that culminates in the translocation of GLI transcription factors to the nucleus, thereby activating target genes involved in cell proliferation. Aberrant GLI1 expression has been associated with increased proliferation in lung adenocarcinoma and other cancers.Objective: To compare GLI1 and Ki-67 protein expression in OKCs associated with NBCCS versus sporadic OKCs.Materials and Methods: We included 13 OKCsp and 9 OKCsy from a children's hospital and university ... Immunohistochemistry was performed using anti-GLI1 and anti-Ki-67 to assess GLI1 expression and cell proliferation.Results: No significant differences were observed in GLI1 or Ki-67 expression in the epithelial component of OKCsy versus OKCsp. A positive correlation between GLI1 and Ki-67 expression was detected in the total sample (r = 0.71, p < 0.05).Conclusion: The positive correlation between GLI1 and Ki-67 expression in OKCs suggests an association between SHH pathway activity and cell proliferation in both sporadic and syndromic lesions.
Extramammary Paget disease (EMPD) is an uncommon neoplasm with a predilection for apocrine gland-rich areas, such as the anogenital region. Herpes simplex virus (HSV) commonly causes infection in this location. However, the coexistence of both entities within the same lesion is exceptionally rare.We report the case of an 89-year-old woman presenting with a pruritic erythematous vulvar plaque. Skin biopsy revealed intraepidermal glandular proliferation consistent with EMPD, composed of pagetoid cells positive for CK7 and diastase-resistant periodic acid-Schiff (PAS). In addition, acantholytic areas containing multinucleated giant cells with ground-glass nuclei and positive immunohistochemical staining for HSV were identified. Subsequent investigations showed no evidence of an underlying visceral malignancy.The concomitant occurrence of EMPD and HSV is extremely rare, with this representing the fourth reported case in the literature. This case highlights the importance of recognising superimposed HSV infection in EMPD, as it may alter the histological features and pose a diagnostic challenge.
Mostramos un caso de liposarcoma desdiferenciado retroperitoneal en una mujer de 57años, en el que se detecta un reordenamiento que implica a los genes HMGA2 (12q14.3) y KERA (12q21.33) mediante secuenciación de nueva generación (Next-generation sequencing [NGS]), un reordenamiento no descrito previamente.
Human T-lymphotropic virus type 1 (HTLV-1) is associated with immune dysregulation, opportunistic infections, and, less commonly, lymphoproliferative and inflammatory disorders. We report the case of a young woman presenting with acute appendicitis, hyperkeratotic skin lesions, onychodystrophy, and subsequent facial diplegia. Investigation revealed HTLV-1 infection and crusted scabies, supporting an underlying immunosuppressed state. Histopathological examination of the appendix showed a transmural, angiocentric lymphocytic infiltrate involving small- and medium-sized vessels, without fibrinoid necrosis or leukocytoclasia. Immunohistochemical analysis demonstrated a predominance of CD4+ T lymphocytes with low proliferative index, consistent with a reactive process. These findings support a diagnosis of lymphocytic vasculitis presenting as acute appendicitis. Although a causal relationship cannot be definitively established, the clinicopathological and immunophenotypic features suggest a potential association with HTLV-1 infection, which has not been previously reported in this setting.
Angiosarcoma is a highly malignant endothelial neoplasm that accounts for 1-2% of all soft tissue sarcomas in humans, and its marked biological aggressiveness constitutes a major clinical challenge. Early identification is particularly difficult in patients with a history of malignancies treated with radiotherapy, due to its histopathological heterogeneity and nonspecific clinical presentation, which often leads to confusion with other mesenchymal or epithelial neoplasms. We report the case of a 72-year-old woman with a history of cervical carcinoma treated with radiotherapy who presented with progressive pelvic pain, significant weight loss, and urinary symptoms. Initial imaging studies suggested peritoneal carcinomatosis, while multiple biopsies were negative for tumour recurrence. Given the discordance between morphological findings and initial immunohistochemical studies, a stepwise diagnostic approach using immunohistochemical panels was implemented. This approach confirmed peritoneal angiosarcoma following demonstration of CD31 positivity. This case highlights the importance of maintaining a high index of suspicion in patients with a history of pelvic irradiation, the utility of sequential diagnostic algorithms, the limitations of resource-limited settings, and the value of a multidisciplinary approach in the management of rare sarcomas.
The accurate categorisation of histopathological images is crucial for the reliable identification of morphologically similar cancers, including lung and colon cancer. According to the WHO and IARC, lung cancer accounted for approximately 2.48 million new cases and 1.8 million deaths worldwide in 2022, making it the leading cause of cancer-related mortality worldwide. Colorectal cancer also represents a major global health burden, with more than 1.9 million new cases and approximately 930,000 deaths reported in 2020 alone. These rising burdens highlight the need for robust computational pathology systems capable of accurate morphological discrimination. In this paper, we propose MorphoViT-CNN, a hybrid model that combines a Vision Transformer for capturing global contextual information with Convolutional Neural Networks (CNNs) for extracting fine grained local features. A morphology-aware segmentation module is designed to incorporate cellular shape, size, and texture attributes, while self-distillation improves the consistency of internal representations without requiring external supervision. Supervised contrastive learning further enhances inter-class separability, particularly in label-limited settings. The model was evaluated on the LC25000 dataset using five-fold cross validation, and ablation studies were conducted to assess the contribution of each component. MorphoViT-CNN demonstrated superior accuracy and precision-recall performance compared with leading CNN and transformer-based baselines, while significantly reducing misclassification among challenging histological subtypes. Its interpretable and multi-scale architecture provides a scalable framework for integration into computational pathology workflows. Future work will explore multimodal integration and foundation model pre-training to further enhance its applicability to precision oncology.
We report a case of retroperitoneal dedifferentiated liposarcoma in a 57-year-old woman, in which a rearrangement involving the HMGA2 (12q14.3) and KERA (12q21.33) genes was detected by next-generation sequencing (NGS), a previously unreported rearrangement.
Bilateral testicular tumours are uncommon, and synchronous presentations involving different histogenetic lineages are rarely reported in the literature. Most bilateral tumours are metachronous and of germ cell origin. The coexistence of a malignant germ cell tumour in one testis and a benign sex cord-stromal tumour in the contralateral testis is an unusual finding with diagnostic and therapeutic implications. We present the case of a 45-year-old man who underwent bilateral radical orchiectomy after ultrasonography identified three nodules in the left testis (maximum diameter 24mm) and a 7mm lesion in the right testis, with tumour markers within normal ranges. Histopathological examination showed a multifocal classic seminoma confined to the left testis and a Leydig cell tumour confined to the right. Immunohistochemical analysis confirmed distinct lineages. This case highlights the importance of thorough histopathological evaluation in guiding clinical management.
BACKGROUND:Microscopic colitis is a well-defined entity comprising two histopathological subtypes: lymphocytic colitis and collagenous colitis, which may represent different stages of the same disease. Upper gastrointestinal involvement by a process sharing histological features with microscopic colitis appears to be much more uncommon, and its pathogenesis, clinical significance, and management remain poorly characterised in the literature, as it may be easily overlooked or mistaken for other entities. PATIENTS AND METHODS:We retrospectively reviewed a series of patients with collagenous gastritis diagnosed at a large tertiary hospital serving a population of over 500,000 inhabitants in the metropolitan area of Madrid, Spain. Between 2010 and 2023, only seven gastric biopsy specimens were diagnosed as collagenous gastritis, corresponding to five patients. RESULTS:All patients were women, aged 21-38 years. They presented with non-specific symptoms, and endoscopy revealed only mild nodularity in one case. Random gastric biopsies established the diagnosis of collagenous gastritis. None of the patients had associated collagenous colitis, collagenous enteritis or coeliac disease. Only one patient underwent long-term follow-up with sequential biopsies, which demonstrated persistent histological changes over time while the patient remained asymptomatic. CONCLUSIONS:A recent systematic review identified 101 patients with collagenous gastritis presenting with heterogenous clinical profiles and an overall favourable prognosis, even in the absence of specific treatment. It remains unclear whether collagenous gastritis represents a distinct clinicopathological entity or merely a residual histopathological finding, as there are no clear-cut clinical or endoscopic features that allow reliable suspicion of this disease.
INTRODUCTION:Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a rare benign lesion that can mimic malignant neoplasms. CASE PRESENTATION:A 19-year-old woman presented with long-standing seizures and severe headache. Magnetic resonance imaging revealed a giant intra-axial mass (8.3cm) in the right hemisphere with calcifications and mass effect, suggestive of a high-grade glioma. Complete surgical resection was performed. Histopathological examination showed a fibrillary stroma with abundant dystrophic calcifications, without atypia or mitotic figures. Immunohistochemistry demonstrated positivity for GFAP and S100 and negativity for EMA in the lesion, with a low proliferative index (Ki-67 <1%), confirming CAPNON. CONCLUSION:CAPNON is an important differential diagnosis of calcified lesions. Although its radiological appearance may be aggressive, it is a benign lesion, and complete surgical resection is usually curative.
HCG groups (hyperchromatic crowded groups) are hyperchromatic cellular aggregates observed during routine screening for cancer and premalignant intraepithelial lesions in both negative and abnormal cervical cytology samples. This study aimed to characterise the cytomorphological features of HCG groups in cervical cytology samples, in order to classify them as benign/reactive, atypical, or potentially neoplastic, and to explore their clinical significance in this setting. Conventional cervical cytology samples that were satisfactory for analysis and exhibited HCG groups were selected. Of 2810 cytological cases, 70 (2.49%) met the inclusion criteria. HCG groups were identified in 41% of negative cytology samples and in 59% of abnormal samples. Atypical HCG groups (ASC-H) were the most common (24.28%), followed by potentially neoplastic/HSIL (17.14%). The morphology of HCG groups is variable, necessitating carefully recognition, differentiation, and interpretation, particularly in abnormal cases requiring detailed and systematic evaluation. In cases with a clear HSIL context, the presence of HCG groups composed of squamous metaplastic cells or cells with a glandular appearance may raise suspicion of intracanal HSIL, which should be confirmed by histopathological examination. Comprehensive assessment of both cellular and background features in cytological smears helps clarify the origin of HCG groups, ensuring accurate morphological characterisation and appropriate cytological classification and clinical interpretation. Clinical and epidemiological information is essential for the accurate classification of HCG groups.
Mesenteric cysts are uncommon lesions whose classification is primarily based on their histological origin. We present the case of a mesenteric cyst diagnosed incidentally during staging investigations for colonic adenocarcinoma. Histological examination revealed a multiloculated cystic lesion lined by non-mucinous columnar epithelium without atypia, associated with mature pancreatic acini. Immunohistochemical analysis showed positivity for CK7, CK19, EMA, and trypsin, and negativity for mesothelial, enteric, and lymphatic markers, thereby excluding the subtypes described in current classifications. This exceptional finding, not previously reported, broadens the histopathological spectrum of mesenteric cysts and suggests pancreatic heterotopia as a possible origin of a subtype not recognised to date.
OBJECTIVE:To determine the time spent by technical staff in the anatomical pathology department on each of the processes in which they were involved, and to define a workload unit. METHODS:The time required for technical procedures was measured over 5 days in 10 hospitals. The median time for each process was calculated. RESULTS:The time required for registration was 3.92min/specimen; for embedding of small specimens, 1.96min/specimen; for embedding of large specimens 10.91min/specimen; for microtomy, 1.01min/specimen; for immunohistochemistry, 2.13min/specimen; for liquid-based cytology, 4.02min/specimen; and for archiving, 0.49min/specimen. CONCLUSIONS:The technical workload unit (TWU) is set at 11min, corresponding to the rounding of 10.91min/specimen for large-specimen embedding, as this is the most time-consuming task. Thus, TWU values range from 0.09TWU/specimen for block preparation and sectioning to 1TWU/specimen for large-specimen embedding.
Rosai-Dorfman disease (RDD) is an infrequent non-Langerhans cell histiocytosis characterised by the proliferation of histiocytes with emperipolesis. Although extranodal involvement accounts for 43% of cases, gastrointestinal involvement is uncommon (<1%), making isolated ileal disease extremely rare. We report the case of a 66-year-old male presenting with intestinal obstruction preceded by constitutional symptoms. Capsule endoscopy demonstrated an ulcerated, stenosing lesion in the distal ileum, resulting in capsule retention and requiring surgical intervention. Histopathological examination confirmed RDD and excluded IgG4-related disease. This case illustrates the diagnostic challenge of extranodal RDD, which must be considered as a differential diagnosis in gastrointestinal lesions with atypical behaviour, to ensure timely management and prevent complications associated with delayed diagnosis.
BACKGROUND:Adenoid cystic carcinoma (AdCC) of the salivary glands is an aggressive tumour that can resemble other basaloid or biphasic neoplasms, particularly when only focally represented. We evaluated the diagnostic and prognostic utility of engrailed homeobox 1 (EN1) and MYB immunohistochemistry. METHODS:Eighty-eight archival tumours, including 42 AdCC and 46 non-AdCC, were analysed. EN1 and MYB expressions were scored from 0 to 6, and positivity was defined as a score of ≤4. Associations between clinicopathological parameters and survival curves were assessed using Kaplan-Meier analysis. RESULT:Follow-up data were available for 40/42 AdCC, with a median PFS of 22.3 months. EN1 was positive in 41/42 AdCC (97.6%) and was associated with adverse clinicopathological features and outcomes, including recurrence and death. MYB was positive in 36/42 AdCC (85.7%) and was associated with angioinvasion and high-grade transformation. Among other tumour types, EN1 showed high specificity for epithelial-myoepithelial carcinomas, basal cell adenomas, and cellular pleomorphic adenomas, although it was more frequently positive in polymorphous adenocarcinomas. Conversely, MYB demonstrated greater specificity in distinguishing AdCCs from polymorphous adenocarcinomas. The difference in MYB expressions between AdCCs and polymorphous adenocarcinomas was statistically significant (p=0.0042). CONCLUSION:EN1 is a highly sensitive marker for AdCC and has prognostic value. MYB is a useful complementary marker, particularly when polymorphous adenocarcinoma is a consideration.
INTRODUCTION:Osteosarcomas (OS), the most common primary malignant bone tumours, are classified as low-grade (characterised by MDM2 amplification) or high-grade (with complex karyotypes). Accurate diagnosis is essential for treatment and prognosis. This study evaluates pre-analytical variables associated with the success or failure of epigenetic analyses in osteosarcoma samples and proposes a standardised preparation protocol. METHODS:Retrospective cohort study of adult patients with OS diagnosed at our sarcoma reference centre (CSUR) over the past 20 years. Pre-analytical variables: year of diagnosis, histological subtype, tissue type, site of origin, sample type (core needle biopsy or surgical specimen with or without chemotherapy), decalcification method (none, EDTA, or nitric acid), and FISH availability. Five 5-μm sections were obtained from each paraffin block. DNA methylation profiling was performed using the Infinium MethylationEPIC v2.0 platform (Illumina). Univariate and multivariate analyses were performed to identify failure predictors. RESULTS:A total of 103 samples from 79 patients were analysed: 58 conventional OS, 14 extraskeletal, 24 parosteal, and 7 dedifferentiated OS. Of the 95 formalin-fixed, paraffin-embedded (FFPE) samples, 43 (45.2%) were suitable for epigenetic analysis, whereas all frozen samples were adequate (100%). Decalcification affected success rates, although not significantly: nitric acid was associated with the highest failure rate (68.97%), followed by EDTA (57.14%) and non-decalcified samples (46.15%). CONCLUSION:FFPE samples are suitable for epigenetic studies, although performance depends on pre-analytical factors. Frozen tissue remains the gold standard. Nitric acid should be avoided. A protocol is proposed that prioritises frozen tissue, documents decalcification methods, excludes strong acids, incorporates quality control measures, and favours samples less than five years old.
Mycosis fungoides (MF) remains a diagnostic challenge in its early stages, due to its ability to mimic common inflammatory dermatoses and the subtlety of its histopathological features. This review integrates recent advances in anatomical pathology and molecular research, highlighting how the combined assessment of morphology, immunophenotype, clonality studies and emerging high-throughput platforms is reshaping our understanding of the disease. Transcriptomic analyses, microRNA profiling and spatial technologies reveal distinctive signatures of early-stage MF, along with microenvironmental and immune alterations that precede clinically evident progression. These findings not only enhance diagnostic accuracy but also help identify patients at higher risk of disease progression. Overall, the integration of clinical, histopathological, and molecular data is defining a new paradigm for refined prognostic stratification and precision-medicine approaches in cutaneous T-cell lymphomas.
The clinical application of cancer stem cell marker CD44 in breast cancer prognosis has been widely explored. However, data on the association between CD44 expression and prognostication across molecular subtypes of breast cancer remain limited. In this study we evaluated CD44 expression in various breast carcinoma subtypes and its association with clinicopathological prognostic parameters. Further, molecular docking studies were performed to investigate molecular interactions involving CD44. A cross-sectional study was conducted on breast tissue specimens collected from 60 patients over a period of two years. Immunohistochemistry analyses were performed to assess CD44 expression in paraffin-embedded breast tissue samples. Clinicopathological prognostic parameters were analysed in relation to CD44 expression. Of the 60 cases, CD44 staining was positive in 34 cases (57%) and negative in 26 (43%). Increased CD44 expression was correlated with histological grade (p=0.022), lymphovascular invasion (p=0.039), and lymph node status (p=0.033) in invasive breast carcinoma. Notably, high CD44 expression was also observed in patients with triple-negative breast cancer. Further, protein docking analysis revealed significant interactions between CD44 and molecular markers such as ER, PR, HER2/neu, and Ki-67, with HER2/neu showing the strongest correlation. Several new targeted treatments for breast cancer were also identified through docking studies. These findings highlight that induced CD44 expression could be a potential marker of aggressive tumour behaviour in invasive breast carcinoma and across multiple molecular subtypes, including triple-negative breast cancer.
