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Primary renal myoepithelial carcinoma is an exceedingly rare neoplasm with an aggressive phenotype and Ewing sarcoma breakpoint region 1 (EWSR1) rearrangement in a small fraction of cases. In addition to its rarity, the diagnosis can be challenging for the pathologist due to morphologic heterogeneity, particularly on the biopsy specimen. At times, immunohistochemistry may be indecisive; therefore, molecular studies should be undertaken for clinching the diagnosis. We aim to illustrate a case of primary myoepithelial carcinoma of the kidney with EWSR1-rearrangement in a 67-year-old male patient who presented with right supraclavicular mass, which was clinically diagnosed as carcinoma of an unknown primary. An elaborate immunohistochemical work-up aided by fluorescent in-situ hybridization allowed us to reach a conclusive diagnosis. This unusual case report advocates that one should be aware of the histological mimickers and begin with broad differential diagnoses alongside sporadic ones and then narrow them down with appropriate ancillary studies.

Background Synovial sarcoma (SS) is a malignant mesenchymal neoplasm with variable epithelial differentiation, with a propensity to occur in young adults. The pathognomonic t(X;18) chromosomal translocation and subsequent development of the SS18:SSX fusion oncogenes are the driver of the distinct genomic features. Aim To study the Clinicopathological, immunohistochemical and molecular features of SS occurring in all the organ systems. Method A retrospective observational study was conducted over a period of 4 years at a tertiary cancer centre. Result One hundred eight patients were included in the study based on exclusion and inclusion criteria. The median age of patients was 30.5 years and mean tumor diameter was 10.5 cm. Most common site was lower limb followed by lung, and arm. 50 patients underwent surgery and 49 patients received adjuvant chemotherapy or radiotherapy. 87 patients (81%) presented with monophasic subtype and 21 (19%) with biphasic subtype. The most helpful immunohistochemical markers for diagnosis and exclusion of close differentials were TLE1, EMA, Pancytokeratin, S-100, BCL2, and CD99. Molecular diagnostic confirmation was attained in 10 out of 15 patients. On median follow-up of 7.58 months, mean 4-year overall survival of the patients was 91.39%. Conclusion Meticulous pathologic evaluation and awareness of the typical and atypical histology of SS along with the apt application of immunohistochemical marker such as TLE1 and/or cytogenetics (SYT translocation) assist in precise recognition of this not so common entity. The main therapeutic modality is surgical excision with negative margins, with the addition of radiotherapy and/or chemotherapy based on patient and tumour characteristics.

HER2-positive metastatic breast cancer (MBC) represents a challenging subtype of breast cancer, characterized by aggressive disease and poor clinical outcomes. Trastuzumab emtansine (TDM1), an antibody–drug conjugate combining trastuzumab and emtansine, has demonstrated efficacy in clinical trials as a second-line treatment for patients progressing after prior therapies. This study aims to provide real-world evidence on the efficacy and safety of TDM1 in HER2-positive MBC patients. A retrospective analysis was conducted on 70 HER2-positive MBC patients treated with TDM1 at our centre between January 2020 and December 2022. Clinical characteristics, progression-free survival (PFS), overall survival (OS), response rates, and toxicity were evaluated using hospital records. PFS and OS were calculated using Kaplan–Meier methods, and survival curves were compared with log-rank tests. The median age of patients was 47 years, with a majority presenting with advanced disease and prior treatment lines. The median PFS was 6.1 months (95% CI, 4.5–7.6), and the median OS was 14.4 months (95% CI, 10.2–18.0). The objective response rate was 75.7%, with 12.8% achieving a complete response and 62.8% a partial response. PFS was significantly longer in hormone receptor-positive patients compared to hormone receptor-negative patients (8.1 vs. 4.1 months, p = 0.035). Toxicity was manageable, with grade 3–4 adverse events including elevated transaminases (8.5%), thrombocytopenia (5.7%), and anemia (4.2%). The efficacy of TDM1 in this real-world cohort aligns with clinical trial data, though PFS and OS were somewhat lower compared to trials, likely due to the inclusion of patients with more extensive disease and prior treatments. Notably, TDM1 demonstrated activity against CNS metastases and a manageable safety profile, with higher incidence of hepatic and hematologic toxicities. Our study supports the use of TDM1 as a viable option for treating HER2-positive MBC in routine clinical practice, confirming its effectiveness and safety profile observed in clinical trials.

Background Solitary fibrous tumor (SFT) is a distinct fibroblastic tumor that can occur at any anatomical site and can manifest a variety of histopathological features. NAB2-STAT6 gene fusion has recently emerged as a sensitive and specific molecular marker and its surrogate on immunohistochemistry, STAT6 has also displayed considerable efficacy. Nevertheless, its histologic diversity can result in diagnostic challenges, especially when classic features are not apparent. Methods A retrospective study was conducted at a tertiary cancer centre in North India over 3 years to document the clinicopathologic and immunomorphologic profile of SFTs. Immunohistochemical analysis of BCOR and p53 were gauged additionally and patients were stratified according to Modified Demicco and Salas criteria for risk of metastasis. Results Sixteen patients of SFT were identified, affecting middle-aged men and women equally. Though lung/pleura are known to be involved commonly, SFT affects other sites such as the kidney, brain, buccal mucosa, liver, and penis as well. The majority endured localized disease while a lesser number suffered locoregional/distant spread. Two patients revealed features of a malignant profile. Risk stratification according to the Modified Demicco and Salas criteria evinced comparable results. No discernible relationship however was highlighted between the immunohistochemical expression of BCOR, p53, and any significant SFT parameter. Conclusion Although SFTs are very rare substantially benign mesenchymal neoplasms, pathologists must be conversant with their histological diversity and be vigilant of their malignant attributes. The worth of STAT6 immunohistochemistry for precise diagnosis and long-term studies for delineating clinical behavior cannot be overemphasized.

Background Thyroid nodules, whether benign or malignant, are commonly identified as palpable or incidental findings. Accurate diagnosis is critical, with fine-needle aspiration cytology (FNAC) playing a crucial role in distinguishing between benign and malignant lesions. The Bethesda System for Reporting Thyroid Cytopathology (BSRTC) standardizes FNAC reporting and estimates the risk of malignancy (ROM), aiding treatment decisions. This study aims to determine the risk of malignancy for each category of the Bethesda System and to evaluate the sensitivity and specificity of FNAC in diagnosing thyroid swellings. Methodology Clinicopathological data of thyroid FNAC and corresponding thyroid resection cases, collected over four years at the Department of Oncopathology, Mahamana Pandit Madan Mohan Malviya Cancer Centre and Homi Bhabha National Institute, Varanasi, were analyzed. Results A total of 559 patients (372 females, 187 males) with a median age of 49 years were evaluated. Among the BSRTC categories, Category VI (32.4%) and Category II (29.2%) were the most common. ROM for each category was as follows: 50%, 25%, 30%, 85.71%, 97%, and 100%, respectively. FNAC demonstrated a sensitivity of 98%, a specificity of 64%, a positive predictive value of 96%, and a negative predictive value of 75%. Concordance between cytopathological and histopathological findings for malignant cases was 69.8%. Papillary thyroid carcinoma was the most common malignancy. Conclusions The ROM for categories I, II, and III was significant, highlighting the importance of the six-tier reporting system. The BSRTC system standardizes reporting and clinical management. Our data, primarily from an oncology center, may vary based on the expertise of the pathologist, laboratory setup, and patient demographics.

IntroductionThe revision of International Federation of Gynaecology and Obstetrics staging in 2018 with recommendations to include cross-sectional imaging and a separate stage for node positive disease have opened a lot of uncertainties in implementing the correct treatment approach in these patients. While studies have suggested higher chances of occult para-aortic lymph node (PALN) even with advanced imaging, especially in pelvic node positive disease which tend to recur after pelvic radiation therapy. This study intends to study these patients and isolate the subset who will benefit most from elective PALN irradiation.Methods and analysisThis is an ongoing multicentric phase III randomised controlled trial with a sample size of 274 subjects in two arms (137 in each arm) to determine the superiority of limited elective para-aortic irradiation compared with no irradiation. Arm one includes radiation to the lower PALN and pelvis; Arm two includes radiation to the pelvis. Concurrent chemotherapy followed by brachytherapy is standard in both arms. Patients with cervical cancer and radiologically positive pelvic LNs aged>18 years and<70 years are screened for the study. The primary endpoint of this study is 3-year disease-free survival. The secondary endpoints include 3-year para-aortic recurrence-free survival, 3-year distant metastasis-free survival, 3-year overall survival, acute and late toxicity, quality of life. Translational study to evaluate systemic immune response by FAPI-PETCT (fibroblast activator protein inhibitor positron emission tomography) and assessment of p16, L1 cell adhesion molecule (L1CAM) and protein death ligand-1 (PDL-1) expression by immunohistochemistry.Ethics and disseminationThe study has been approved by the institutional ethics committee and will be routinely monitored according to standard guidelines. The results of the study will be published in peer-reviewed scientific journals, presented at conferences and submitted to regulatory authorities.Trial registration numberThe study was registered on 17 January 2022 under CTRI/2022/01/039495 (http://ctri.nic.in).

Background Metaplastic breast cancer with heterologous mesenchymal differentiation, known earlier as carcinosarcoma, consists of both infiltrating ductal carcinoma cells and mesenchymal cells, and is associated with an aggressive course. The mesenchymal component is rarely endothelial, with only two previously reported cases. The present case is the third among those. Moreover, the disease outcome was good, unlike the usual course of carcinosarcoma. Case presentation A 59-year-old multiparous woman of Indo-aryan ethnicity developed a lump in her left breast and was diagnosed with breast carcinosarcoma having an endothelial component, with the help of histopathological examination and immunohistochemistry. The tumor was surgically removed; then the patient received adjuvant chemotherapy, epirubicin, and cyclophosphamide, followed by adjuvant radiotherapy to the whole breast, followed by tumor bed boost. The patient was clinic-radiologically disease-free even at 26 months post-treatment. Conclusion Surgery followed by adjuvant chemotherapy and radiotherapy gives better outcomes compared with surgery alone, with a doubtful role of neoadjuvant chemotherapy. Targeted therapies can be considered in patients not responding to conventional treatment.

Background Ovarian sex cord-stromal tumors (OSCSTs) represent a rare and heterogeneous group of neoplasms originating from the ovarian sex cords and stroma. These tumors account for approximately 5–7% of all ovarian cancers. They encompass a diverse array of histopathological subtypes and exhibit significant histomorphological diversity, which underpins their varied clinical presentations and biological behaviors. The authors embarked on this study to chronicle the clinical presentation, the myriad histologic miens of OSCSTs, the associated diagnostic pitfalls and utilitarian pearls, treatment strategies, and outcomes of these patients. Methods A retrospective analysis was conducted on patients diagnosed with OSCSTs at a tertiary cancer care center in North India from July 2019 to June 2023, over a period of 4 years, with due approval from the Institutional Ethics Committee. Results Thirty-five patients with OSCSTs were identified, affecting 88.6% adults and 11.4% children or adolescents. The predominant symptoms were abdominal pain (65.7%) and distension (42.8%). Bilateral ovarian involvement was ascertained in 42.8% of cases, and metastasis was detected in 34%, predominantly in the omentum/peritoneum. The most common histological type was adult granulosa cell tumors, followed by fibromas, Sertoli-Leydig cell tumors, juvenile granulosa cell tumors, and steroid cell tumors. These tumors manifested a confounding variety of histomorphologic facets, resulting in consideration of wide-ranging differential diagnoses. Early-stage (stage I) disease was diagnosed in 57.7% of cases, while 42.3% presented at advanced stages (stages III and IV). There were no significant differences in histopathological features across the stages; however, higher stages correlated significantly with disease progression. Over a median follow-up period of 36 months, the overall 5-year survival rate was 95.5% ± 4.4%, with a mean survival time of 66.2 months. Conclusion OSCSTs exhibit a wide range of histopathological features and predominantly present at an early stage, with a high overall 5-year survival rate. However, advanced-stage OSCSTs can behave erratically clinically, necessitating the prediction of such occurrences. Pathologists must be conversant with the histologic diversity and be vigilant in avoiding misdiagnosis. The role of a multidisciplinary focus on developing efficacious models for risk assessment stratification cannot be overemphasized.

IntroductionMetaplastic breast cancer (MBC) is a rare malignancy that accounts for < 1% of all breast cancers. The aim of this study is to evaluate the clinicopathologic characteristics of MBC patients treated at a tertiary cancer center.Materials and methodsIn this study, the authors retrospectively analyzed the prospectively maintained data of MBC patients treated at a tertiary cancer care center in North India between January 2019 and July 2022.ResultsA total of 28 MBCs were identified. The median age of presentation was 47 years (range 27-81 years). Seventeen patients (60.7%) presented with clinical T3/T4 disease, and axillary nodal involvement was detected in 11 patients (39.3%) at presentation. Two patients had metastatic disease at presentation. A preoperative diagnosis of MBC on core biopsy was attained in five patients (17.9%), and the most common histologic subtype was sarcomatoid carcinoma. Triple-negative receptor status was observed in 15 patients (53.6%). Six patients (21.4%) underwent upfront breast conservation surgery and another six (21.4%) upfront mastectomy. Thirteen patients (46.4%) underwent mastectomy following neoadjuvant therapy. Definitive axillary nodal metastasis was found in eight patients (32%). Following neoadjuvant chemotherapy, five patients (35.7%) had stable disease, disease progression was evident in five patients (35.7%), partial response in four patients (28.6%), and no patient evinced complete response. Adjuvant postoperative radiation therapy was administered in 16 patients (57.1%). At a median follow-up of 13.2 months (range 4-26 months), 16 patients (57.1%) were alive with no evidence of disease, one patient (3.6%) was alive with disease, nine patients (32.1%) died of disease, and two patients (7.2%) died of other causes. One patient suffered from locoregional recurrence and nine patients developed distant metastasis.ConclusionMBC is an infrequent entity among breast carcinomas in India, which is similar to the reports of MBC worldwide. The diagnosis of MBC is difficult and requires the use of immunohistochemistry. Most of the cases in our study presented with a larger tumor size; however, they displayed a relatively lower incidence of nodal involvement as well as hormone receptor negativity. Being a rare and heterogeneous disease, large-scale studies are essential for better understanding and management of these tumors.

Carcinosarcomas of the salivary gland with osteosarcoma component are very rare, with only 17 cases reported. Despite multiple poor prognostic factors, our patient's outcome was favorable, highlighting the importance of early diagnosis and aggressive treatment in improving prognosis for this aggressive tumor variant.