Frequency of Programmed Death Receptor Ligand 1 Expression and Clinicopathological Factors Associated With Metastatic Triple-Negative Breast Cancer at a Tertiary Cancer Care Centre in South India.

Purpose Triple-negative breast cancer (TNBC) has a poor outcome compared to other subtypes. Immune checkpoint inhibitors (ICIs) have changed the treatment paradigm in metastatic diseases as well as in neoadjuvant setting. The response to these agents is affected by programmed death ligand 1 (PDL1) receptor expression which are reported objectively as a score. PDL1 is a prognostic marker also. Here, we present clinicopathological characteristics of metastatic TNBCs, report the proportion of PDL1 expression and its association with clinicopathological factors as well as survival. Methods This is a prospective study carried out at a tertiary cancer care centre in South India. Case records of all breast cancer patients treated in two years between August 2021 and July 2023 were reviewed, patients with metastatic TNBC were selected. Patient's characteristics, histological features, molecular profile, and treatment were analyzed. PDL1 testing was carried out on pretreatment tumor tissue sections with immunohistochemistry (IHC) (Dako 22C3). PDL1 staining was interpreted as negative or positive based on combined positive score (CPS), with an expression less than 10 considered negative. Results A total of 118 patients were analyzed. With a median age of 46 years (36-65 years), 52.5% (62/118) were premenopausal. Family history of Ca Breast was seen in 22% (26/118) patients. A majority of patients had left-sided tumor 55.9% (66/118). Visceral metastasis was more common 96.6% (82/118) than skeletal. Radical intent of treatment was adopted in 10% as patients had oligometastatic disease at presentation. As front-line treatment, anthracycline-based chemotherapy was administered to the majority 54.2% (64/118). The PDL1 expression with CPS more or equal to 10 was seen in 32.2% (38/118) patients. Survival was associated with menopausal status (p value=0.000) and family history (p value=0.028) but not with PDL1 nor sidedness in our study. Estimated survival at 12 months in PDL1 negative case is 10 ± 0.29 months, while in PDL1 positive case it is slightly more at 10 ± 0.75 months, but difference was not found to be statistically significant (p value=0.15). Conclusion TNBCs are highly aggressive subtype with limited treatment options and poorer outcomes. Our study shows PDL1 expression in 31.66% of the cases similar to other literature from India. Survival is associated with menopausal status and family history. No association was found between survival and PDL1 as well sidedness in our study.

Mortality Audit of Cancer Patients in the Department of Medical Oncology at a Tertiary Cancer Care Centre in South India.

Considerable advances in the diagnosis and treatment of cancer have made a huge impact on morbidity and mortality from neoplastic diseases. However, cancer remains the leading cause of death across the world. This is a retrospective study carried out at a tertiary cancer care centre (Kidwai Memorial Institute of Oncology, Bangalore) in South India. Case records of all cancer patients who died while receiving inpatient treatment between January 2022 and December 2022 under the Department of Medical Oncology were reviewed and studied. There was a total of 240 deaths. Out of these, the majority of deaths 147 (61.25%) were patients with haematological malignancies while the remaining 93 (38.75%) were patients with solid tumours. In patients with solid tumours, the majority 49 (52.7%) were in the age group of 40 to 60 years while only 18 (19.35%) patients were less than 40 years. The majority of patients were male sex i.e. 55(59.1%) and undergoing treatment with palliative intent 81 (87%). The most common organ was the lung in 21 patients (22.6%) followed by the breast while the most common system involved was the gastrointestinal tract in 28 (30.1%) patients. The most frequent cause of death was progressive disease in 72 (77.4%) while sepsis (11 patients; 11.8%) was the second most frequent cause of death in solid tumours. In haematological malignancies, also a significant number of 57 (38.8%) patients were in the age group of 40 to 60 years. Fifty-two (35.3%) patients were in the age group of 22 to 40 years. The majority were male sex (79 patients; 53.7%). About the phase of treatment, the majority of deaths 45 (30.6%) were during induction and under evaluation. Those with relapse/refractory disease were 38 (25.9%). A substantial number of patients had acute myeloid leukaemia 47 (32%) and five (3.4%) deaths were acute promyelocytic leukaemia patients. Twenty-three patients (15.6%) had acute lymphoblastic leukaemia. The most common cause of death was sepsis in 76 patients (51.7%) while intracranial bleeding was in 34 patients (23.1%). In some patients, there were multiple causes leading to death. Mortality audits are important to evaluate the services being provided at any centre. One can appreciate the lacunae in handling a particular disease or flaws in a treatment protocol or the staff delivering the treatment. Sepsis is the leading cause of death in patients with haematological malignancy; even in solid malignancy sepsis accounts for a substantial proportion of deaths and should be handled aggressively to save lives.

Adenomyoepithelial adenosis mimicking phylloides: A diagnostic dilemma.

Benign proliferative breast diseases are well recognized in young females. Benign biphasic proliferation of epithelial and myoepithelial cells has been observed, among which adeno-myoepithelial adenosis is one of the rare morphologies published in the literature with the tendency to recur and poses a risk for low-grade malignant transformation. Here, we report a case of a young female who had a history of recurrent breast lump mimicking phyllodes tumor and eventually diagnosed as adeno-myoepithelial adenosis on histopathological examination. Benign proliferative breast diseases are well recognized in young females. Benign biphasic proliferation of epithelial and myoepithelial cells has been observed, among which adeno-myoepithelial adenosis is one of the rare morphologies published in the literature with the tendency to recur and poses a risk for low-grade malignant transformation. Here, we report a case of a young female who had a history of recurrent breast lump mimicking phyllodes tumor and eventually diagnosed as adeno-myoepithelial adenosis on histopathological examination.

Understanding the Impact of Population and Cancer Type on Tumor Mutation Burden Scores: A Comprehensive Whole-Exome Study in Cancer Patients From India.

PURPOSE: The purpose of this study was to understand the impact of population diversity and geographic variation on tumor mutation burden (TMB) scores across cancers and its implication on stratification of patients for immune checkpoint inhibitor (ICI) therapy. MATERIALS AND METHODS: This retrospective study used whole-exome sequencing (WES) to profile 1,233 Indian patients with cancer across 30 different cancer types and to estimate their TMB scores. A WES-based pipeline was adopted, along with an indigenously developed strategy for arriving at true somatic mutations. A robust unsupervised machine learning approach was used to understand the distribution of TMB scores across different populations and within the population. RESULTS: The results of the study showed a biphasic distribution of TMB scores in most cancers, with different threshold scores across cancer types. Patients with cancer in India had higher TMB scores compared with the Caucasian patients. We also observed that the TMB score value at 90th percentile (predicting high efficacy to ICI) was high in four different cancer types (sarcoma, ovary, head and neck, and breast) in the Indian cohort as compared with The Cancer Genome Atlas or public cohort. However, in lung and colorectal cancers, the TMB score distribution was similar between the two population cohorts. CONCLUSION: The findings of this study indicate that it is crucial to benchmark both cancer-specific and population-specific TMB distributions to establish a TMB threshold for each cancer in various populations. Additional prospective studies on much larger population across different cancers are warranted to validate this observation to become the standard of care.

Application of the Milan System for Reporting Salivary Gland Lesions and Its Cytohistological Correlation for Risk Stratification: A Single-Institution Experience.

INTRODUCTION:  Salivary gland tumors are known to have a heterogeneous profile with variable clinical presentation and a wide variety of histological subgroups of prognostic significance. Immunocytochemical markers that aid in the diagnosis and characterization of the cell type of origin are critical for this heterogeneous group of malignancies. AIMS AND OBJECTIVES: To study the application of The 'Milan System' for Reporting Salivary Gland Cytology and the diagnostic utility of a panel of immunocytochemical markers in the diagnosis of salivary gland neoplasms and their cytohistological correlation for their risk stratification. MATERIALS AND METHODS: This was a prospective study carried out in which a total of 60 patients were enrolled in the study. Fine-needle aspiration cytology (FNAC) smears and cell blocks were prepared with standard techniques and staining procedures. Immunocytochemistry (ICC) was performed on cell block sections by immunoperoxidase procedure. Immunocytochemical (ICC) stains were used for the differentiation of the lesions in cell blocks. Histopathology was also studied if the patient underwent excision of salivary gland lesions. DISCUSSION AND RESULTS: Almost 60 cases were studied under FNAC and cell block evaluation, as well as ICC, among those five (8.33%) samples were inadequate, eight (13.3%) were non-neoplastic, 27 (45%) were benign, one (1.7%) was neoplasm with uncertain malignancy potential, one (1.7%) was suspected of malignancy, and 19 (31.7%) were malignant. The histopathological diagnosis was confirmed in 47 cases. Of these, 24 (51.1%) were benign and 23 (48.9%) were malignant. The malignancy rate for Milan Categories I, II, III, IVa, IVb, V, and VI was 0%, 0%, 100%, 24%, 50%, 80%, and 84.6%, respectively. The study showed that malignancy risk stratification could be further improved by using cell block with immunocytochemistry as a complementary diagnostic modality. CONCLUSIONS: The present study was carried out to assess the usefulness of the Milan system to report salivary gland cytology results. Thus, the findings of the present study show that the Milan system is helpful in stratifying the risk of malignancy in salivary gland tumors.

Expression of immune checkpoint protein in oral squamous cell carcinoma and its clinicopathological correlation: A tertiary care center cross-sectional study.

Background: Recent evidence suggests that oral squamous cell carcinoma (OSCC) patients who exhibit the immunohistochemical expression of immune checkpoint protein programmed cell death ligand 1 (PD-L1) are more likely to have a poor clinical outcome and may serve as an independent prognostic marker. Aims and Objectives: This study aimed to assess the immunohistochemical expression of immune checkpoint protein PD-L1 in OSCC and its clinicopathological correlation. Materials and Methods: OSCC cases were included in the study. This was a tertiary care center cross-sectional one-year duration study. Histomorphological diagnosis and immunohistochemical expression of PD-L1 were performed after taking ethical clearance. The statistical analysis was performed using Statistical Package for Social Sciences (SPSS) version 21.0 statistical analysis software. Results: A total of 106 cases of OSCC were included in the study. Histologically, the majority of cases (58.5%) were graded as well differentiated, followed by moderately differentiated (58.5%) and poorly differentiated (4.7%), respectively. In PD-L1 immunohistochemical expression, score 1+ was accorded to 37 (34.9%), 2+ was accorded to 31 (29.2%), and score 3+ was accorded to 33 (31.1%) cases. Tumor size, pattern, depth of invasion lymphovascular invasion (LVI), and perineural invasion (PNI) were found to be significantly associated with PD-L1 immunohistochemical scores. Conclusions: We concluded that the immunohistochemical expression of immune checkpoint protein PD-L1 positivity in tumor cells was seen in the majority of the cases (60.37%) in our patient. This suggests that the PD-1 or PD-L1 pathway plays a significant role in tumor immune evasion in OSCC.

Guanidino quinazolines and pyrimidines promote readthrough of premature termination codons in cells with native nonsense mutations.

Using small molecules to induce readthrough of premature termination codons is a promising therapeutic approach to treating genetic diseases and cancers caused by nonsense mutations, as evidenced by the widespread use of ataluren to treat nonsense mutation Duchene muscular dystrophy. Herein we describe a series of novel guanidino quinazoline and pyrimidine scaffolds that induce readthrough in both HDQ-P1 mammary carcinoma cells and mdx myotubes. Linkage of basic, tertiary amines with aliphatic, hydrophobic substituents to the terminal guanidine nitrogen of these scaffolds led to significant potency increases. Further potency gains were achieved by flanking the pyrimidine ring with hydrophobic substituents, inducing readthrough at concentrations as low as 120 nM and demonstrating the potential of these compounds to be used either in combination with ataluren or as stand-alone therapeutics.

Promising role for pleural vent in pneumothorax following CT-guided biopsy of lung lesions.

OBJECTIVES: To evaluate the safety, effectiveness and cost-benefit of ambulatory pleural vent compared to conventional chest drain for pneumothorax following CT-guided biopsy of lung lesions (CTGB). METHODS: We retrospectively analysed electronic hospital records of patients requiring intervention for pneumothorax following CTGB. All patients treated with pleural vent over a 2-year period (August 2017-July 2019) were included and compared to a control group of all patients treated with chest drain over a previous 2-year period (August 2014-July 2016). RESULTS: Patients managed with a pleural vent had a shorter length of hospital stay compared to the chest drain group (median 0 days vs 4.5 days, p < 0.01). The mean cost of follow-up in the pleural vent group was £530.36 per patient compared to a mean of £2699.38 per patient in the chest drain group (p-value < 0.01). CONCLUSION: Pleural vent can be a safe and effective alternative to conventional chest drain for the management of CTGB-related pneumothorax which allows patients to be managed on an outpatient basis with reduced hospital stays and lower associated healthcare costs. ADVANCES IN KNOWLEDGE: To the best of our knowledge, this is the first study demonstrating the safety and effectiveness of pleural vent for CTGB-related pneumothorax.

Osteoclastic variant of anaplastic thyroid carcinoma: An insight into a rarest of rare entity.

Anaplastic thyroid carcinoma is a rare and a very aggressive thyroid malignancy with a dismal prognosis. It has a short history and presents with a rapidly increasing neck mass associated with compressive symptoms like pain, hoarseness of voice, dysphagia and shortness of breath. Osteoclastic variant is an extremely rare variant, which is, characterize by presence of a large number of multinucleated giant cells, which resemble osteoclasts. Here we report two cases of this unusual variant in a 68 years old and 49 years old male with a short history of thyroid swelling.

Comparison Between CHOP and DAEPOCH with or Without Rituximab in Adult High Grade B Cell Lymphoma, Not Otherwise Specified; A Retrospective Study From a Tertiary Cancer Hospital in South India.

Lymphoma that on morphology appear blastoid or intermediate between DLBCL and BL but who lack myc and bcl-2 and/or bcl-6 rearrangements are grouped under high grade B-cell lymphoma, not otherwise specified (HGBL, NOS). Only a few studies have yet compared the outcome of HGBL, NOS treated with different chemo-immunotherapy regimens. HGBL, NOS patients were analyzed retrospectively, who were treated with CHOP or DAEPOCH regimens every 21 days for six cycles with or without rituximab. The primary clinical objective was progression free survival. One and two year PFS rates were 29.4% and 20.6% for the CHOP arm and, 65.2% and 47.8% for the DAEPOCH arm respectively. There was statistically significant difference in mean PFS between the arms (DAEPOCH vs CHOP: 19.7 months vs 12.8 months; HR = 0.44, p = 0.02, 95% CI: 0.22-0.88). One and two year OS rates were 91.1% and 20.5% for the CHOP arm and 95.6% and 60.8% for the DAEPOCH arm respectively. Mean OS was significantly better for DAEPOCH arm (28.1 months vs 20.7 months: HR = 0.43, p = 0.03, 95% CI: 0.20-0.92). Grade 3 and 4 hematological and non-hematological toxicities were more common in DAEPOCH arm. There were 2 treatment related deaths, 1 in each arm (4.3% for DAEPOCH vs 2.9% for CHOP). HGBL, NOS is a heterogeneous group of aggressive lymphoma associated with early relapse in nearly half of the cases. Intensive regimens like DAEPOCH is associated with improved outcome in terms of PFS and OS. Though toxicities are more with DAEPOCH, they are manageable and treatment related mortality is low.

PD-1 and PD-L1 Expression in Indian Women with Breast Cancer.

OBJECTIVE: The interaction between programmed cell death protein 1 (PD-1) on activated T-lymphocytes and programmed death-ligand 1 (PD-L1) on tumor cells or antigen-presenting cells sends immunosuppressive signals leading to the escape of tumor cells from the host anti-tumor immune response. Inhibiting this interaction with antibodies against PD-1 or PD-L1 is emerging as a valuable therapeutic strategy. However, tissue distribution patterns for PD-L1 and PD-1 in breast cancer patients from India are not reported, yet many clinical trials are underway. In this study the expression of PD-1 and PD-L1 in breast cancer patient samples from India was characterized. MATERIALS AND METHODS: The study included 392 cases of operated breast cancer (2012-2017) from a tertiary cancer care center in Bangalore, Karnataka, India. Paraffin blocks were retrievable and receptor status was known. Immunohistochemistry (IHC) was performed using anti-PD-L1 and anti-PD-1 antibodies. RNA was isolated from 76 fresh tumors and nine adjacent normal tissues (2019). PD-L1 transcript levels were measured by RT-qPCR using Hypoxanthine-guanine phosphoribosyl transferase (HPRT) as a reference gene. RESULTS: Based on IHC, PD-1 expression within tumor-infiltrating immune cells (TIICs) was observed in 55/385 cases (14%) across all breast cancer types. In triple-negative breast cancer (TNBC), 21/132 cases (16%) showed PD-1 staining in TIICs. The overall expression of PD-L1 in breast tumor cells across all breast cancer subtypes and TIICs was 11% (41/378) and 39% (151/385), respectively. A relatively higher proportion of TNBC cases had PD-L1 expression in tumor cells (17/132 cases, 13%) and immune cells (68/132 cases, 52%). We also detected PD-L1 transcript expression by qRT-PCR in freshly isolated tumor samples. CONCLUSION: These findings show that around 52% (68/132) of the TNBC cases express PD-L1 in TIICs. Hence, anti-PD-1/PD-L1 therapy alone or combined with chemotherapy may be a promising treatment for TNBC in Indian patients.

3D-bulk to nanoforms of modified hydroxyapatite: Characterization and osteogenic potency in an in vitro 3D bone model system.

Synthetic bioceramics are replacing conventional methods of treating bone defects with autografts owing to the high demand of bone substitutes, with their Surface topography and size contributing to favor cytocompatibility in tissue regeneration. This experimental study deals with the comparative evaluation of the physical characterizations of four different in-house synthesized bioceramics from 3D-bulk to nanoforms of hydroxyapatite (HA), Biphasic calcium phosphate (BCP), Strontium doped hydroxyapatite (SrHA) and Silica coated hydroxyapatite (HASi) and also simultaneously evaluates adhesion, proliferation and osteogenic differentiation of rabbit adipose derived mesenchymal stem cells (RADMSCs) on these biomimetic ceramic niches. The osteogenic induced cells grown on 3D scaffolds for a period of 7, 14, 21, and 28 days were analyzed for their viability (MTT, LDH, live-dead assays), morphology (SEM), proliferation (Cytox-Red) and osteogenic differentiation (ALP, osteocalcin expression). Cellular activities and differentiation of RADMSCs were significantly higher on SrHA indicating the role of strontium in the differentiation of mesenchymal stem cells on this ceramic platform to the bone lineage. In order to reinforce the materials for hard tissue implantation and drug delivery, nano-SrHA (nSrHA) became the nanoparticle of choice based on its non-toxicity, cytocompatibility and osteogenic properties (nSrHA > nHASi > nBCP > nHA).

Fixed dose combination of capecitabine and cyclophosphamide in metastatic breast cancer: Results from THE ENCLOSE phase 2/3 randomized multicenter study.

AIM: To evaluate pharmacokinetics, efficacy and safety of fixed-dose combination (FDC) of oral capecitabine + cyclophosphamide in metastatic breast cancer (MBC) patients progressing after anthracycline and/or taxane chemotherapy. METHODS: In this prospective, adaptive, phase-2/3, open-label study (CTRI/2014/12/005234), patients were randomized (1:1:1) to three FDC doses (doses/day: D1, capecitabine + cyclophosphamide 1400 mg + 60 mg; D2, 1800 mg + 80 mg; D3, 2200 mg + 100 mg) for 14 days, in 21-day cycles. In Part-I, multiple-dose pharmacokinetics and optimal dose(s) were evaluated with futility analysis. Group(s) with <3 responders based on best overall response rate (BOR, complete response [CR]+partial response [PR]), were discontinued. Efficacy (BOR, disease control rates [DCR; CR + PR + stable disease]) and safety of optimal dose(s) were evaluated in Part-II. RESULTS: Of 66 patients (n = 22/group) in Part-I, pharmacokinetics (D1 = 7/22, D2 = 9/22, D3 = 8/22) showed dose-proportionality for cyclophosphamide and greater than dose-proportionality for capecitabine. Modified intent-to-treat (mITT) analysis showed BOR of 7.14% (1/14) in D1 (discontinued), and 22.22% (4/18) each in D2 and D3, respectively. In Part-II, 50 additional patients were randomized in D2 and D3 (n = 144; total 72 [22 + 50] patients/group). mITT analysis in D2 (n = 54) and D3 (n = 58) showed BOR of 29.63% (16/54, 95%CI: 17.45-41.81%) and 22.41% (13/58, 95%CI: 11.68-33.15%), respectively. DCR in D2 and D3 were 87.04% (47/54, 95%CI: 78.08-96.00%) and 82.76% (48/58; 95%CI: 73.04-92.48%) after 3 and 57.41% (31/54; 95%CI: 52.41-79.50%) and 50.00% (29/58; 95%CI: 40.40-67.00%), after 6-cycles, respectively. Hand-foot syndrome (16.67%), vomiting (9.72%) in D2, and hand-foot syndrome (18.06%), asthenia (15.28%) in D3 were most-common adverse events. CONCLUSION: FDC of capecitabine + cyclophosphamide (1800 + 80 mg/day) showed high disease control rates and good safety profile in MBC patients.

Metastatic hormone receptor-positive breast cancer in CDK 4/6 era: An outcome audit.

BACKGROUND: The treatment landscape of metastatic hormone receptor (HR) positive breast cancer has been changed in recent years. Availability of CDK 4/6 inhibitor and other hormone therapy has changed the treatment algorithm for these patient, we retrospectively analyzed our metastatic HR positive breast cancer patients. MATERIALS AND METHODS: In this study, we retrospectively analyzed the case records of hr positive metastatic breast cancer patient treated at department of medical oncology from October 2016 to September 2018. Demographical characteristics, site of metastasis, objective response and clinical benefit response and toxicity profile were analyzed. RESULTS: We treated a total of 178 patients of MBC with HT at our center during the study period. One hundred fifty-two patients received HT alone (control group) and 26 patients received HT and CDK 4/6 inhibitor (study group). The median age of patients was 56 and 58 years in the control group and study group. The ORR was 41.7 versus 57.9 (95% CI [1.01-2.56]), and the CBR was 66.1% versus 78.9%; (CI [1.18-3.56]) (P < 0.05) of the patients in control and study groups, respectively. CONCLUSIONS: Among patients with HR-positive, advanced breast cancer, hormone therapy is efficacious addition of CDK 4/6 inhibitor improve the efficacy with tolerable side effects.

Primary squamous cell carcinoma, breast: A challenging diagnosis.

BACKGROUND: Primary squamous cell carcinoma of the breast is an extremely rare malignancy constituting less than 0.1% of all breast cancers with very few cases reported in literature. It is an aggressive, triple-hormone negative tumor, and its appropriate management is still debated. It is diagnostically challenging on both histopathology as well as radiology. Different diagnostic criteria are established for its definite diagnosis. As squamous cells are not found normally in the breast, various theories have been proposed regarding its origin. But the exact pathogenesis is still unclear. We report one such case encountered. CASE: A 54-year-old female presented with gradually progressive painless lump in the right breast for 3 months with no other clinical features. There was neither any history of chronic or malignant disease in the patient nor in her family. On clinical examination, there was well-defined, firm and nontender swelling in upper inner quadrant measuring 3 × 2 cm with overlying skin being normal. There was no swelling in the contralateral breast as well as in the bilateral axillary region. A suspicion of malignancy was raised on initial core needle biopsy and, on repeat biopsy, was diagnosed as metaplastic carcinoma with squamous differentiation. Later, on final resection, specimen was reported as primary squamous cell carcinoma of the breast without any nodal metastasis. All the metastatic causes were ruled out through proper clinical, radiological, and histopathological correlation. CONCLUSION: Primary squamous cell carcinoma of the breast is an aggressive tumor with its treatment protocol being still unclear, owing to its rarity. It is important to rule out the metastatic causes. It is relatively resistant to conventional chemotherapy, and its prognosis is also unpredictable. Hence, this requires further studies in terms of management and prognosis.

Can intermittent fasting be helpful for knee osteoarthritis?

Obesity and Knee Osteoarthritis (KOA) has a proven association. The obese individuals are likely to have early and more severe KOA, and the complications and overall results of surgery are also inferior. Hence, weight reduction is of paramount importance for these individuals. Due to the inability to do intense physical activities, these individuals cannot lose weight and instead perpetually kept gaining weight. Hence, intermittent fasting as a non-operative means of weight reduction is an attractive and viable option. This review article would help sensitize the Orthopaedic Surgeons about fasting in weight reduction and assisting the KOA. Hence, the choice of intermittent fasting should be offered to obese patients with KOA for weight reduction.

Effect of the Noninvasive Follicular Thyroid Neoplasm With Papillary-Like Nuclear Features (NIFTP) Nomenclature Revision on Indian Thyroid Fine-Needle Aspiration Practice.

OBJECTIVES: To analyze risk of malignancy (ROM) in Bethesda categories (BCs) and the impact of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) reclassification on malignancy risk and surgical outcome. METHODS: In this retrospective study based on fine-needle aspiration samples with histologic follow-up, ROM was analyzed in BCs. Possible cases of NIFTP were reviewed, followed by the analysis of impact of this reclassification on ROM in BCs. RESULTS: The incidence of NIFTP was 6.9% among excised thyroid nodules and 16.8% among all resected neoplastic lesions. ROM for BCs I to VI was 37.5%, 9.6%, 40.0%, 46.5%, 88.8%, and 96.8%, respectively. Risk of neoplasia was 50.0%, 13.8%, 55.0%, 71.2%, 88.8%, and 96.8% respectively. When NIFTPs were considered nonmalignant lesions, ROM decreased by 6.3%, 4.3%, 20%, 19.1%, 22.5%, and 1.5% in each Bethesda category (I-VI), respectively. Inability to diagnose NIFTP preoperatively led to overtreatment in 16.2%. CONCLUSIONS: Prevalence of NIFTP in Asian countries may be higher than expected. Substantial cases of NIFTP have a benign preoperative cytology; hence, cases of follicular adenoma and adenomatous colloid nodule should be included in the review. NIFTP reclassification has significantly reduced the ROM in indeterminate BCs, suggesting diagnostic lobectomy rather than total thyroidectomy. Countries should establish their own malignancy risk range and parameters.

Diagnostic Relevance of GATA 3 Expression in Urinary Bladder Carcinoma of Divergent Differentiation and Other Histological Variants.

GATA binding protein 3, a zinc finger transcription factor, has now been demonstrated as a valuable and sensitive marker for conventional urothelial carcinoma with sparse literature related to its expression in various histological variants. It is a prospective study where 74 consecutive cases of bladder carcinoma were included between August 2016 and January 2017 followed by immunohistochemistry to assess GATA 3 expression in conventional as well as different urothelial carcinoma (UC) variants. Overall, 57 of the 74 lesions (77%) demonstrated nuclear staining for GATA 3. GATA 3 expression significantly correlated with histological grade (P < 0.001) and muscle invasion (P = 0.005). Divergent differentiation was observed in 54% (40/74) of the total cases. The study included 12 different variants of urothelial carcinoma. All or majority of the cases of clear cell (6/6, 100%), glandular (6/8, 75%), and sarcomatoid (4/6, 66.7%) variants expressed GATA 3 in a moderate to strong fashion and belonged to group III or IV. Nested variant, small cell carcinoma, pure squamous cell carcinoma, and squamous component of urothelial carcinoma with squamous differentiation do not show any GATA 3 expression. GATA 3 was expressed more intensely as well as in greater number of tumor cells at lymph node metastatic tumor deposits as compared to the primary tumor. GATA 3 expression was not significantly associated with tumor stage or patients' clinical outcomes. GATA 3 is expressed in majority of variants of UC albeit with variable staining; however, situation is challenging in some variants known to be associated with poor prognosis like nested variant, small cell carcinoma, and squamous cell carcinoma where it is not expressed. Hence, the sensitivity of this determinant is diminished in these variants, which may affect the interpretation of GATA 3 stains at metastatic sites as well as their distinction from secondary bladder involvement, by tumors of non-urothelial origin.

Cystic adrenal lesions: A report of five cases.

BACKGROUND: Cystic adrenal lesions are rare and uncommon manifestation with few cases reported so far. Different types of adrenal cysts have been described with heterogeneous etiology and overlapping clinical findings, ranging from benign to malignant cystic neoplasm. They are usually asymptomatic or may rarely present with abdominal pain or fullness. Optimum management of adrenal cysts still remain controversial, owing to its low incidence. In this study, we report our institutional experience on diagnosis and management of different histological types of cystic adrenal lesions. CASES: During 4 years period, 55 patients underwent adrenalectomy with five cases presenting as adrenal cysts. All the five patients were biochemically nonfunctional and underwent adrenalectomy (laparoscopic anterior n = 2, retroperitoneoscopic approach n = 1, and open anterior transperitoneal approach n = 2). The primary indications for surgery were larger size and/or suspicion of malignancy. Histological evaluation revealed two epithelial cysts, one endothelial cyst, one pseudocyst, and a very rare case of adrenocortical carcinoma arising in a pseudocyst. CONCLUSION: Cystic adrenal lesions are rare with varied etiologic and clinical presentation that may sometimes lead to diagnostic and management dilemma. These cases must undergo biochemical and radiological evaluation to rule out underlying malignancy followed by referral for surgical intervention.