OBJECTIVE:Synovial sarcoma usually presents with spindle cell morphology with or without epithelial differentiation. Extensive rhabdoid differentiation is a very rare feature with only few cases described in literature. CASE REPORT:We present two cases of synovial sarcoma with rhabdoid differentiation along with their clinical follow-up. Both cases had tumor in the vicinity of joints and showed lung metastasis during follow-up inspite of R0 resection. CONCLUSION:We emphasised that extensive rhabdoid differentiation can be deceptive and challenging for diagnosis in small biopsies and also show an aggressive clinical course with dismal prognosis. Awareness of this rarely described unusual and aggressive histomorphological subtype is prudent due to its distinct diagnostic, prognostic and therapeutic implications.

Round cell sarcoma with EWSR1::PATZ1 fusion is an extremely rare sarcoma of soft tissue and bones that comes under EWSR1::non-ETS fusion sarcoma. Molecular studies, such as next-generation sequencing, are essential for accurate diagnosis, as this tumor presents as conventional round cell sarcoma, often co-expressing myogenic and neurogenic markers, which can prompt an erroneous diagnosis of rhabdomyosarcoma (RMS) or malignant peripheral nerve sheath tumor. Due to the rare incidence and paucity of literature on this tumor, the definite prognostic implications and therapeutic guidelines are lacking. Here, we describe two patients with EWSR1::PATZ1 sarcoma, of which one patient was initially misdiagnosed as synovial sarcoma and RMS on two occasions. These patients underscore the diagnostic challenges and therapeutic uncertainties surrounding EWSR1::PATZ1 fusion sarcomas, emphasizing the need for further large collaborative studies to establish optimal prognostic implications and management strategies for this rare entity.

AIMS:Anaplastic lymphoma kinase (ALK) rearrangements are actionable drivers in non-small cell lung carcinoma (NSCLC), but the biological significance of ALK-immunohistochemistry (IHC) positivity in high-grade pulmonary neuroendocrine carcinoma (NEC) remains unclear. This study evaluated the diagnostic and therapeutic implications of discordant ALK IHC and genomic findings and the role of multimodal molecular testing in resolving them. METHODS:We retrospectively analysed eight South Asian patients (Indian and Nepali) with de novo high-grade pulmonary NEC and diffuse ALK immunoreactivity treated at a tertiary cancer centre in India. Comprehensive molecular profiling using DNA- and RNA-based next-generation sequencing (NGS) and ALK fluorescence in situ hybridisation (where tissue was adequate) was performed. Clinical outcomes and responses to ALK-targeted tyrosine kinase inhibitors (TKIs) were assessed. RESULTS:ALK IHC positivity was observed in 8 of 100 selectively tested cases among 319 high-grade pulmonary NECs diagnosed between 2019 and 2025. The cohort included seven SCLCs (one combined adenocarcinoma-SCLC) and one large-cell neuroendocrine carcinoma (LCNEC). Median age was 51 years; 75% were female and 87.5% never-smokers. Among five comprehensively profiled cases, true ALK rearrangements were confirmed in two (one LCNEC and one SCLC), both detectable only by RNA sequencing. Durable benefit from ALK-TKI therapy was seen only in the molecularly confirmed LCNEC case (>16 months), whereas ALK IHC-positive but NGS-negative cases progressed rapidly. CONCLUSIONS:True ALK rearrangements in high-grade pulmonary NEC are rare but highly actionable. ALK IHC alone is an unreliable predictor of therapeutic benefit. RNA-based sequencing is essential for fusion detection. Comprehensive molecular confirmation, with RNA sequencing as the preferred modality, should precede any initiation of ALK-targeted therapy in high-grade pulmonary NEC.

Histopathologically detected extranodal extension leads to upstaging and treatment escalation in head and neck squamous cell carcinoma. There is considerable variation in the prevalence of histopathologically detected extranodal extension in comparable studies. The Head and Neck Cancer International Group, which includes 23 organisations managing patients with head and neck cancer, identified several challenges in evaluating histopathologically detected extranodal extension. Thus, the Head and Neck Consensus Language for Ease and Reproducibility (HN-CLEAR) and its global stakeholders prioritised developing diagnostic criteria and uniform terminology for histopathologically detected extranodal extension. The histopathologically detected extranodal extension working group established by WHO, International Collaboration on Cancer Reporting, American Joint Committee on Cancer, Union for International Cancer Control, North American Society of Head and Neck Pathology, and American Academy of Oral and Maxillofacial Pathology committees undertook consensus deliberations using scanned whole slides and a PRISMA literature review-based scoping questionnaire. The guidelines were tested by 30 additional pathologists across six continents and strengthened with prescriptive diagnostic criteria and unifying terminology based on the inter-rater concordance analyses. This Review generates practically useful consensus diagnostic recommendations and aligned terminology for addressing the gaps in the histopathologically detected extranodal extension literature. The recommendations can be used globally and cater to all levels of medical resources, practices, and experiences, thus ensuring equitable patient care.

Worst pattern of invasion (WPOI) has been evaluated in many single-institute cohorts. Our goal was to perform a large multicentre evaluation of WPOI as a prognostic marker in oral squamous cell carcinoma (OSCC). Retrospective pathology data was collated from 14 institutions and compared with clinical outcome in 1374 OSCC patients with upfront curative resection. Most cases were of oral tongue (n = 645, 47%); T2 (33%) and N0 (59%). WPOI 1-3 frequency was 29.4%, WPOI 4 47% and WPOI 5 22%. On univariable analysis, the 3-year disease free survival (DFS) was 54.2% for WPOI 5 vs. 69.7% for WPOI 1-4 (p < 0.001). The locoregional control (LRC) was 68.9% vs 79.2% (p = 0.001), and overall survival (OS) 68.4% vs 83.8% (p < 0.001). On multivariable Cox-regression in the entire cohort, WPOI 4 or 5 was strongly correlated with other known poor prognostic factors and not an independent predictor of OS (HR 1.10, 95% CI 0.92-1.52), LRC or DFS. However, in early-stage (pT1-2 N0) patients treated with surgery alone without adjuvant radiotherapy, WPOI 5 was a robust independent predictor of DFS (HR 4.36, 95% CI 1.54-12.32, p = 0.006), OS (HR 3.69, 95% CI 1.23-11.1, p = 0.020) and LRC (HR 3.52, 95% CI 2.13-5.82, p <0.001) after applying inverse probability weighting to correct for selection bias. Furthermore, in the entire cohort of early-stage patients, interaction modeling showed that adjuvant radiotherapy significantly reduces the risk for both DFS and LRC for those with WPOI-5 (Interaction p = 0.002). Therefore, it may act as a predictive biomarker for the benefit of adjuvant radiotherapy. The prognostic and predictive role of WPOI-5 should be validated in prospective trials.

Human epidermal growth factor receptor type 2 (HER2) is overexpressed in 15–20

We report a case of young female in her 20s who presented with a supraclavicular soft tissue mass. Diagnostic biopsy showed a malignant round cell tumor with areas of spindling and hyalinized stroma. The utilization of an immunohistochemistry panel revealed positive results for NKX2.2 and CD99 expression. This positivity led to the consideration of a differential diagnosis of Ewing sarcoma, EWSR1::NFATC2- rearranged sarcoma, and mesenchymal chondrosarcoma for further assessment. On further immunohistochemistry with NKX3.1 and EWSR1 break-apart fluorescent in situ hybridization analysis, a diagnosis of mesenchymal chondrosarcoma was rendered which was later on confirmed with biphasic histology on excision specimen. NKX3.1 is a useful immunohistochemistry marker to resolve the differentials when dealing with undifferentiated small round cell sarcoma of bone and soft tissue, especially on a needle biopsy.

Extranodal extension (ENE) is a major adverse factor in head and neck squamous cell carcinoma (HNSCC) and the basis for recommending adjuvant chemoradiotherapy (CRT). The independent prognostic role of ENE subtypes, however, remains unclear when other pathological features are considered. We retrospectively studied 320 surgically treated patients with pathologically ENE-positive HNSCC (2018–2024). ENE was classified as microscopic (ENEmi, ≤ 2 mm) or macroscopic (ENEma, > 2 mm) as per AJCC. Overall survival (OS) and disease-free survival (DFS) were primary endpoints. Multivariable Cox regression, propensity score matching (PSM), and receiver operating characteristic (ROC) analysis were performed. Of 320 patients, 194 (60.6

Extranodal extension (ENE) increases the risk of recurrence and death in head and neck squamous cell carcinoma (HNSCC) patients and is an indication for treatment escalation. Histopathology forms the mainstay of diagnosing ENE. There is substantial variation in the diagnosis of ENE and related terminology. Harmonising the diagnostic criteria for ENE was identified as a priority by the Head and Neck Consensus Language for Ease of Reproducibility (HN CLEAR) Steering Committee and its global stakeholders. An international working group including 16 head and neck pathologists from eight countries across five continents evaluated whole slide images of haematoxylin and eosin-stained sections depicting potential diagnostic problems through nine virtual meetings to develop consensus guidelines. ENE should be diagnosed only when viable carcinoma extends through the primary lymph node (LN) capsule and directly interacts with the extranodal host environment with or without desmoplastic stromal response. Identifying the original LN capsule and reconstruction of its contour can assist in the detection and assessment of ENE. The term matting is recommended for confluence of two or more nodes due to histologically identifiable tumour extending from one LN to another. Matting constitutes major form of ENE. On the other hand, the terms fusion/adhesion/confluence/conglomeration and other synonyms of adhesion should be limited to confluence due to fibrosis or inflammation without histologically identifiable tumour between involved lymph nodes. Tumour extension along narrow needle tracks or spillage of cyst contents following an FNA do not constitute ENE. The consensus recommendations encompassing the definition of ENE, macroscopic and histologic examination of lymph nodes (LN) and practical guidelines for handling challenging cases are provided.

With the advent of next-generation sequencing, increasingly we can sub classify the soft tissue sarcomas into various subtypes with distinct prognostic and therapeutic implications. Sarcomas with RAF1 mutations are extremely rare and so far, the treatment strategies are not known. Here, we report a case of a 48-year-old lady who initially presented with right ear swelling, which was excised and was suggestive of dermatofibrosarcoma protuberans with S100 expression. After a disease-free interval of 25 months, the patient relapsed with metastasis in the lung. Repeat biopsy and next-generation sequencing (NGS) were suggestive of PDZRN3/RAF1 fusion mutated sarcoma. On presentation, the patient had an Eastern Cooperative Oncology Group performance status of 4 and had respiratory distress due to lung metastasis. After consensus and decision in the molecular tumour board, the patient was started on low-dose trametinib and doxorubicin. After three cycles of treatment, the patient had a partial response and post six cycles she had a near-complete response. This case exemplifies the value of molecular characterisation of soft tissue sarcoma and adds to the already sparse literature for RAF1 mutated sarcomas.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a highly sensitive modality for the detection and characterization of breast lesions, yet its limited specificity and interpretative variability pose diagnostic challenges. The American College of Radiology Breast Imaging Reporting and Data System (ACR BI-RADS) provides a structured lexicon but lacks definitive guidance for certain lesion categories, particularly nonmass enhancements. The Kaiser score (KS), a semiquantitative decision-support tool, has emerged as a potential adjunct to standard interpretation and offers a structured approach to improve diagnostic accuracy. The study was aimed to evaluate the diagnostic performance of DCE-MRI of the breast by applying the KS in the characterization of mass and nonmass enhancement and its comparison with ACR BI-RADS. Two radiologists assessed the KS and ACR BI-RADS on 103 sequential patients on 3-T DCE-MRI with 142 histopathologically verified lesions. The diagnostic performance of the KS was recognized through receiver operating characteristic (ROC) by the area under the ROC curve (AUROC). Cohen's kappa coefficient was used to evaluate the inter-reader agreement. These findings were compared and correlated with ACR BI-RADS. The KS has sufficiently high AUROC for all the lesions including mass and nonmass lesions (0.895, 0.955, and 0.622, respectively). The sensitivity of the KS was similar to that of ACR BI-RADS for both readers (93.6–91.5%) with a higher specificity of 85.4% compared with 62.5% for ACR BI-RADS. The improvement in specificity was also seen for mass as well as nonmass lesions. Excellent inter-reader agreement was observed with kappa values of greater than 0.9. DCE-MRI using the KS showed high diagnostic accuracy as compared with ACR BI-RADS with an excellent inter-reader agreement. Thus, the KS in conjugation with ACR BI-RADS can enhance diagnostic accuracy and decrease experience-related variability.

PURPOSE:Over the years, scientific literature has highlighted the importance of depth of invasion (DOI) in managing oral squamous cancers, particularly its association with nodal metastasis. However, determining the role of DOI in postoperative radiation therapy (PORT) remains a clinical challenge. This study aimed to evaluate PORT with a DOI cutoff of 5 mm. METHODS AND MATERIALS:Patients diagnosed with oral tongue squamous cell carcinoma (and restaged as per American Joint Cancer Committee 2018) with pT1,2 and pN0 were selected. Baseline characteristics were collected and divided into 2 groups using a DOI cutoff of ≤5 versus >5 mm. The study endpoints were overall survival (OS), disease-free survival (DFS), and locoregional control (LRC). RESULTS:The study included 255 patients, with comparable baseline characteristics between groups. A significantly higher incidence of perineural invasion (PNI) was noted among patients receiving PORT in both cohorts. After a median follow-up of 37 months, no statistically significant differences were observed in median OS, DFS, or LRC in patients with a DOI ≤5 mm, irrespective of PORT. Conversely, for patients with a DOI >5 mm, the median OS was 48 months for those not receiving PORT, whereas it was not reached for those receiving PORT (P = .03). Furthermore, patients with a DOI >5 mm who received PORT showed significantly improved median DFS and LRC compared with those who did not receive PORT (36 months vs not reached, P = .001 for DFS; 37 months vs not reached, P < .001 for LRC]. In penalized multivariable Cox regression analysis, PORT emerged as the independent prognostic factor for DFS (hazard ratio [HR], 0.50; 95% CI, 0.31-0.82; P = .01) and LRC (HR, 0.34; 95% CI, 0.20-0.60; P < .001) with statistically insignificant OS benefit (HR, 0.58; 95% CI, 0.33-1.02; P = .06) in patients with a DOI >5 mm. CONCLUSIONS:Despite a significantly higher distribution of PNI in patients with DOI >5 mm, the use of PORT significantly improved median OS, DFS, and LRC in this retrospective analysis. The penalized Cox proportional hazard model also suggested that the use of PORT in patients with DOI >5 mm increases survival endpoints irrespective of PNI and lymphovascular invasion positivity, especially for DFS and LRC.

Purpose To investigate the clinical, radiological, histopathological features, survival outcomes, and prognostic factors of the rare primary leiomyosarcoma of bone (PBLMS). Methods This was a retrospective study conducted between the year 2012 to 2022. 16 patients had biopsy-proven PBLMS out of 632 primary bone sarcomas. Data was collected on patient details, tumor characteristics, treatment, and outcomes. Results The study included 12 males and 4 females with a median age of 26.5 years. Common sites were femur (62%), tibia (32%), and humerus (6%). Pathological fractures occurred in 19%. Surgery was the primary treatment- limb salvage in 87.5%, amputation in 12.5% of the patients. Neo-adjuvant chemotherapy was given in 3 patients. Adjuvant chemotherapy and radiotherapy were given in 10 and 2 patients, respectively. One patient had local recurrence. Five patients developed distant metastasis. The 5-year OS and EFS rates were 62.5% and 58.5%, respectively. Higher tumor grade, local recurrence, and distant metastasis adversely impacted OS (p value <0.05). Positive margins, pathological fracture, and distant metastasis negatively affected local recurrence. Conclusions PBLMS is an aggressive sarcoma with high metastatic potential. Early detection and complete surgical resection with negative margins are crucial. The benefit of chemotherapy and radiotherapy remains unclear. Distant metastasis was the most significant adverse prognostic factor for overall survival.

Pulmonary pleomorphic carcinoma (PPC) is a rare, highly aggressive variant of non-small cell lung cancer (NSCLC), comprising 0.1-0.4% of all pulmonary malignancies. While lung cancers typically present with symptoms like cough and hemoptysis, paraneoplastic syndromes are observed in about 10% of cases. Paraneoplastic fever as an initial manifestation is extremely rare. We present a rare case of PPC with neoplastic fever, emphasizing the importance of paraneoplastic syndromes during the evaluation of lung cancer. Surgical resection successfully alleviates neoplastic fever, highlighting the need to recognize paraneoplastic fever as a diagnostic challenge and consider it as a differential in cases of unexplained fever for prompt intervention.

Mesonephric adenocarcinomas (MA) and carcinosarcomas of female genital tract are rare tumors originating from mesonephric duct remnants, which mainly occur in cervix followed by ovarian hilum and broad ligament, and rarely in uterine corpus and lateral wall of vagina. The diagnosis of these tumors is challenging as they exhibit mixture of histomorphological pattern that can be confused with endometrioid, serous, clear cell carcinomas and sex cord stromal tumors of female genital tract. The application of a panel of immunohistochemical markers, which include PAX8, GATA3, TTF1, CD10 and ER, must be applied to reach a correct diagnosis while ruling out the mimickers. Herein, we present four such rare cases with challenging diagnostic features. Molecular analysis performed in 3 cases showed the characteristic KRAS mutation. Due diligence to the morphology and appropriate panel of immunohistochemical markers needed for the accurate diagnosis of MA.

Background Aneurysmal bone cyst (ABC) within the diaphyseal cortex is a very rare finding because most of the ABCs are of metaphyseal origin and within medullary cavity. Imaging of the cortical ABC may be inconclusive; therefore role of biopsy is extremely crucial in pre-operative period for the proper management and surgical plan. Case report A 59-year-old female came to us with complaints of pain and swelling right arm since last 6 months. Radiograph of the involved arm was suggestive of cystic intracortical lesion without fracture. Core needle biopsy report came out to be aneurysmal bone cyst. O-arm and Computer navigation assisted en-bloc resection of the lesion was done as it was involving around half of the cortex and there was risk of iatrogenic fracture in intraoperative and postoperative period if done without navigation. Conclusion O-arm provides real time 3D images which were quite helpful in navigation assisted resection of the lesion so that negative margins can be obtained and maximum cortex of the bone can be saved.

The hobnail subtype of papillary thyroid carcinoma (HSPTC) is a rare and aggressive subtype, comprising 1–2