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Byline: Carolyne. Lallawmzuali, Adil. Khan, Sana. Ahuja, Sufian. Zaheer Synchronous tumors comprising of cortical as well as medullary differentiation are rare in the adrenal gland. Collision tumors comprise of two [...]

Context: The Modified Masood Scoring Index (MMSI) categorizes breast fine needle aspirates into four categories non‐proliferative breast diseases (PBD), PBD without atypia, PBD with atypia and carcinoma in situ/carcinoma. The International Academy of Cytology Yokohama System classifies the aspirates into five categories – inadequate, benign, atypical, suspicious, and malignant. Very few studies have been conducted so far to compare the diagnostic accuracy of this system. Aims: The objectives of the study were to classify breast fine needle aspirates according to the MMSI and IAC Yokohama and assess their risk of malignancy (ROM) and performance parameters. Materials and Methods: All breast FNAs received from June 2020 to May 2023 were classified according to the MMSI and IAC Yokohama. Using histopathological diagnosis as the gold standard, ROM and performance parameters were calculated. Results: Out of the 559 breast fine needle aspirates, the histopathological correlation was available for 337 cases. The ROM for non‐PBD, PBD without atypia, PBD with atypia and carcinoma in situ/carcinoma categories were 0%, 1.2%, 9.1% and 93%, respectively. The ROM for each of the categories of Yokohama system was 16.6%, 1.1%, 4.3%, 86.2% and 97.6%, respectively. The values for the sensitivity, specificity, PPV, NPV and diagnostic accuracy were slightly higher for IAC Yokohama (97.3%, 97.2%, 94.7%, 98.6% and 97.2%, respectively) than the MMSI (96.4%, 96.2%, 93%, 98.1% and 96.3%, respectively). Furthermore, another shortfall of MMSI is the inability to compare the Inadequate category of the Yokohama system. Conclusion: Overall Yokohama system proved to be a better system for categorizing breast lesions on FNAB as the scoring system provides more objective categorization and minimizes false positive and false negative cases. [ABSTRACT FROM AUTHOR]

This study conducts the first meta‐analysis to assess the aggregated risk of malignancy associated with each category of the International System for Reporting Serous Fluid Cytopathology (ISRSFC) for reporting serous effusion cytology, while also evaluating diagnostic accuracy. PubMed/MEDLINE and Embase were systematically searched using the keywords "(pleural, peritoneal, and pericardial effusions) AND (serous effusion cytology) OR (International System for Reporting Serous Fluid Cytopathology)". Articles underwent risk of bias assessment using the QUADAS‐2 tool. After excluding inadequate samples, a meta‐analysis determined sensitivity and specificity for different cutoff points, including "atypical considered positive," "suspicious of malignancy considered positive," and "malignant considered positive." Summary receiver operating characteristic curves assessed diagnostic accuracy, and the diagnostic odds ratio was pooled. Sixteen retrospective cross‐sectional studies, totaling 19,128 cases, were included. Sensitivity and specificity for the "atypical and higher risk categories" considered positive were 77% (95% confidence interval [CI], 68%–84%) and 95% (95% CI, 93%–97%) respectively. For the "suspicious for malignancy and higher risk categories" considered positive, sensitivity and specificity were 57% (95% CI, 49%–65%) and 100% (95% CI, 99%–100%) respectively. Sensitivity and specificity for the "malignant" category considered positive for malignancy were 70% (95% CI, 60%–77%) and 99% (95% CI, 98%–99%), respectively. The pooled area under the curve ranged from 85% to 89.5% for each cutoff. This meta‐analysis underscores the ISRSFC's accuracy in reporting serous fluid cytology. It emphasizes the diagnostic importance of the "suspicious" and "malignant" categories in identifying malignancy, and the role of the "benign" category in ruling out malignancy. This meta‐analysis highlights the accuracy of the International System for Reporting Serous Fluid Cytopathology in reporting serous fluid cytology. It emphasizes the diagnostic significance of the "suspicious" and "malignant" categories in identifying malignancy, as well as the role of the "benign" category in excluding malignancy. [ABSTRACT FROM AUTHOR]

The tumor microenvironment (TME) is a critical determinant in the initiation, progression, and treatment outcomes of various cancers. Comprising of cancer‐associated fibroblasts (CAF), immune cells, blood vessels, and signaling molecules, the TME is often likened to the soil supporting the seed (tumor). Among its constituents, tumor‐associated macrophages (TAMs) play a pivotal role, exhibiting a dual nature as both promoters and inhibitors of tumor growth. This review explores the intricate relationship between TAMs and the TME, emphasizing their diverse functions, from phagocytosis and tissue repair to modulating immune responses. The plasticity of TAMs is highlighted, showcasing their ability to adopt either protumorigenic or anti‐tumorigenic phenotypes based on environmental cues. In the context of cancer, TAMs' pro‐tumorigenic activities include promoting angiogenesis, inhibiting immune responses, and fostering metastasis. The manuscript delves into therapeutic strategies targeting TAMs, emphasizing the challenges faced in depleting or inhibiting TAMs due to their multifaceted roles. The focus shifts towards reprogramming TAMs to an anti‐tumorigenic M1‐like phenotype, exploring interventions such as interferons, immune checkpoint inhibitors, and small molecule modulators. Noteworthy advancements include the use of CSF1R inhibitors, CD40 agonists, and CD47 blockade, demonstrating promising results in preclinical and clinical settings. A significant section is dedicated to Chimeric Antigen Receptor (CAR) technology in macrophages (CAR‐M cells). While CAR‐T cells have shown success in hematological malignancies, their efficacy in solid tumors has been limited. CAR‐M cells, engineered to infiltrate solid tumors, are presented as a potential breakthrough, with a focus on their development, challenges, and promising outcomes. The manuscript concludes with the exploration of third‐generation CAR‐M technology, offering insight into in‐vivo reprogramming and nonviral vector approaches. In conclusion, understanding the complex and dynamic role of TAMs in cancer is crucial for developing effective therapeutic strategies. While early‐stage TAM‐targeted therapies show promise, further extensive research and larger clinical trials are warranted to optimize their targeting and improve overall cancer treatment outcomes. Highlights: Tumor microenvironment (TME) is a critical determinant of tumor behavior.Tumor‐associated macrophages (TAM) plays a crucial role in the TME.TAMs are a diverse population of immune cells that can exhibit different phenotypes or functions.TAMs can switch between different activation states or phenotypes.Numerous preclinical and clinical studies have revealed that targeting TAMs can be an effective approach towards tumor treatment. [ABSTRACT FROM AUTHOR]

Objective: Tuberculosis (TB) remains a major health problem, especially in the developing countries. Fine-needle aspiration cytology is the first line of investigation for tubercular lymphadenitis as it is easy to perform, less invasive, quick, and economical. The typical cytopathological features of tuberculosis TB include epithelioid cell granulomas with Langhans giant cells and caseous necrosis. The present study aimed to evaluate the cytomorphological features of newly diagnosed cases of tubercular lymphadenitis confirmed by GeneXpert. Material and Methods: This was a retrospective study in which all fine-needle aspirates from newly diagnosed cases of tubercular lymphadenitis confirmed by GeneXpert over a 1-year period from July 2022 to July 2023 were included in the study. The May–Grunwald–Giemsa stained smears from these aspirates were categorized into three patterns-epithelioid cell granulomas with necrosis, epithelioid granulomas without necrosis, and necrosis only. The granulomas were further categorized into well-formed, ill--formed, and splintered. The background of the aspirate which included a reactive lymphoid background, lymphocytes, eosinophils, and neutrophils was tabulated for all the cases. Results: Out of the three cytomorphological patterns, epithelioid granulomas with necrosis were the most predominant (67.5%), followed by necrosis only (20.8%) and granulomas without necrosis (11.6%). An acid-fast bacilli (AFB) positivity of 53.3% (64 cases) was seen on the Ziehl-Neelsen stain. Well-composed, poorly formed, and splintered granulomas were seen in 55 (57.9%), 42 (44.2%), and 21 (22.1%) cases, respectively. Neutrophils were the most common background population (42, 35%) followed by lymphocytes (36, 30%). Reactive lymphoid cells and eosinophils were seen in 12 (10%) and 3 (2.5%) cases, respectively. Conclusion: Fine-needle aspiration cytology is a rapid inexpensive minimally invasive test for tubercular lymphadenitis as epithelioid cell granulomas along with caseous necrosis are highly suggestive of TB. However, manual acid-fast AFB detection has a low sensitivity as is illustrated in the present study where only AFBwas demonstrated in only 53.3% of cases. [ABSTRACT FROM AUTHOR]

Physiological embryogenesis and adult tissue homeostasis are regulated by transforming growth factor‐β (TGF‐β), an evolutionarily conserved family of secreted polypeptide factors, acting in an autocrine and paracrine manner. The role of TGF‐β in inflammation, fibrosis, and cancer is complex and sometimes even contradictory, exhibiting either inhibitory or promoting effects depending on the stage of the disease. Under pathological conditions, especially fibrosis and cancer, overexpressed TGF‐β causes extracellular matrix deposition, epithelial–mesenchymal transition, cancer‐associated fibroblast formation, and/or angiogenesis. In this review article, we have tried to dive deep into the mechanism of action of TGF‐β in inflammation, fibrosis, and carcinogenesis. As TGF‐β and its downstream signaling mechanism are implicated in fibrosis and carcinogenesis blocking this signaling mechanism appears to be a promising avenue. However, targeting TGF‐β carries substantial risk as this pathway is implicated in multiple homeostatic processes and is also known to have tumor‐suppressor functions. There is a need for careful dosing of TGF‐β drugs for therapeutic use and patient selection. [ABSTRACT FROM AUTHOR]

Objective: The most important determinant of patient outcome in cases of breast carcinoma is the regional lymph node status. Intraoperative assessment of sentinel lymph nodes (SLNs) allows the surgeon to perform axillary lymph node dissection in the same sitting if required. The commonly performed intraoperative methods for SLN evaluation are touch imprint cytology (TIC) and frozen section. The present study aimed to determine the sensitivity, specificity, and accuracy of TIC with histopathological diagnosis as gold standard. Material and Methods: The lymph nodes sent for intraoperative examination were bisected along the long axis and touched onto clean glass slides followed by Toluidine blue and rapid Papanicolaou staining. The imprints were reviewed and the interpretation was conveyed to the surgeon. Thereafter, the biopsy was fixed in 10% formalin followed by paraffin embedding with hematoxylin and eosin staining. The specificity, sensitivity, diagnostic accuracy, positive predictive value, and negative predictive value were evaluated with histopathological diagnosis as gold standard. Results: A total of 60 patients who underwent resection surgery were included in the study. Majority (36.7%) of patients were in the age group 41-50 years with a mean age of 48.1 ± 10.6 years. There were 54 cases (90%) and 6 cases (10%) of invasive carcinoma of no special type (ductal) and lobular carcinoma, respectively. According to modified Bloom--Richardson scoring, the cases were categorized as Grade 1-6 cases (10%), Grade 2-36 (60%), and Grade 3-18 (30%). The sensitivity and specificity of TIC were 87.5% and 100%, respectively. The diagnostic accuracy of TIC in the diagnosis of metastasis in SLN was 90%. Conclusion: TIC is an easy-to-perform, cost-effective, rapid, and accurate technique for axillary lymph node evaluation, which also overcomes the need for a cryostat. [ABSTRACT FROM AUTHOR]

Tuberculosis of the hypothalamo–pituitary axis is extremely uncommon. The presentation of panhypopituitarism in a case of sellar tuberculosis is an even rarer occurrence. We present a case of a 44‐year‐old man who presented with complaints of headache and right‐sided diminution of vision for six months. A hormone profile showed abnormal anterior pituitary assay suggestive of panhypopituitarism. Magnetic Resonance imaging of the brain showed a sellar mass measuring 1.8 × 1.5 × 1.3 cm with suprasellar extension suggestive of a pituitary adenoma. Histopathological examination showed multiple epithelioid cell granulomas along with Langhans giant cells and mixed inflammatory infiltrates against a necrotic background. Zeihl Neelson stain demonstrated the presence of acid‐fast bacilli. Thus, a final diagnosis of pituitary tuberculoma was made, and the patient started on antitubercular therapy. It is extremely important to correctly diagnose sellar tuberculosis as the treatment is entirely different, and the patient usually responds well to therapy. [ABSTRACT FROM AUTHOR]

Computed tomography is helpful for delineating its intracranial extension or presence underlying bony erosion of the skull base.[4] Fine needle aspiration cytology (FNAC) can act as a more rapid and relatively less invasive modality of diagnosis. A non-contrast-enhanced computed tomography (CT) of the skull revealed an extensive hypodense non-calcified lesion occupying the left nasal cavity and pushing against the lateral nasal wall (Figure 1), suggesting a possibility of olfactory neuroblastoma (also known as esthesioneuroblastoma). Although FNAC is rarely performed in the diagnosis of nasal cavity masses, with preoperative biopsies done instead, in some cases, FNA with the cell block technique and IHC could be used to achieve diagnosis and exclude a malignant process. [Extracted from the article]

Objectives: Fine needle aspiration cytology (FNAC) is a minimally invasive method for sampling a heterogenous lesion. It is one of the first-line investigations in the evaluation of soft tissue tumours. However, the heterogeneity of mesenchymal lesions pose a challenge to the cytological diagnosis. The present study aims at evaluation of the cytomorphological findings of mesenchymal lesions on FNAC along with their histopathological correlation. Material and Methods: This was a retrospective study conducted over a period of 1 year from January 2021 to January 2022. All the patients of cytologically diagnosed mesenchymal lesions on their FNA aspirates were included in the study. Cytomorphology of the May Grunwald Giemsa and Papanicolaou stained slides were examined and correlated with clinical and histopathological details wherever available. Results: Out of the 90 patients, 69 (76.7%) were males and 21 (23.3%) were females. Maximum number of cases were in 4--5th decade of life. The lower limb was found to be the most common site (57.8%) for the mesenchymal lesions. Majority of the cases on FNA in our study were found to be benign -- 79 (87.8%), while only 11 cases were malignant (12.2%). On cytological examination, spindle cell lesions were most common followed by adipocytic lesions. Based on the cyto-histological correlation, sensitivity, specificity, negative predictive value, positive predictive value and diagnostic accuracy of FNAC in diagnosis of mesenchymal lesion was 78.6%, 100%, 92.5%, 100% and 94.1% respectively. Conclusion: FNAC is a simple and minimally invasive tool that plays an important role in triaging patients with good specificity and sensitivity. [ABSTRACT FROM AUTHOR]

Primary neuroendocrine carcinoma (NEC) of the brain is an extremely rare presentation, with only a few previous case reports. We describe a primary NEC arising from the left parieto‐occipital lobe. The 55‐year‐old patient presented with complaints of headache and dizziness for the preceding 7 months. Magnetic resonance imaging revealed a large ill‐defined mass in the left parieto‐occipital lobe, with possible differential diagnosis of meningioma. A craniotomy was performed, and a firm vascular tumor was removed. Histopathological examination revealed a large cell NEC. Immunohistochemistry was performed to exclude the possibility of an extracranial primary. Based on the immunohistochemical expression and absence of any extracranial tumor on positron emission tomography, the diagnosis of primary NEC of the brain was made. It is important to differentiate between primary and metastatic neuroendocrine tumors because they show a significant difference in prognosis and treatment. [ABSTRACT FROM AUTHOR]

Objectives: Tuberculosis (TB) is an important health problem specially in the developing countries. Although effective chemotherapy is available, compliance of patient is a major challenge. The aim of this study was to describe cytomorphological features of drug defaulters on lymph node on fine-needle aspiration cytology (FNAC) and compare it with newly diagnosed cases. Material and Methods: A cross-sectional study was done for a period of 18 months, in which all patients having tuberculous lymphadenitis were included after taking detailed history regarding previous anti-TB drug intake. Cytomorphological findings in drug defaulters were evaluated and compared with newly diagnosed cases. Results: There were a total of 150 cases with 120 newly diagnosed and 30 drug defaulters. Splintered epithelioid cell granuloma was seen in 40% of drug defaulters, while it was absent in case of newly diagnosed cases (P < 0.0001). Well-formed epithelioid cell granuloma was most commonly seen in newly diagnosed cases (65.83%) followed by poorly formed granuloma (26.67%). Another significant finding was distribution of eosinophils which were significantly high in case of drug defaulters (56.67%) (P < 0.0001). Conclusion: Cytomorphological findings can help in identification of the drug defaulters on FNAC and thus plan further line of treatment. [ABSTRACT FROM AUTHOR]

Extraintestinal gastrointestinal stromal tumors (EGISTs) are rare stromal tumors involving mesentery, omentum, and retroperitoneum. EGISTs of the pelvic cavity are extremely uncommon, and till date, no case of pure epithelioid type arising from the pelvic cavity has been reported. They pose a diagnostic pitfall as they may mimic ovarian malignancy. We present a unique case of an epithelioid extraintestinal stromal tumor arising from the pelvic cavity. A 43-43-year-old woman presented with complaints of abdominal pain and menstrual irregularities. Ultrasound examination revealed a large well-defined hypoechoic mass in the right pelvic cavity with a possible site of origin from the right ovary. A total hysterectomy with bilateral salpingo-oophorectomy was done. Histopathological examination revealed an encapsulated tumor comprising predominantly of nests and lobules of epithelioid cells with round-to-oval nuclei, vesicular chromatin, and moderate amount of eosinophilic to clear cytoplasm. Mitotic activity was brisk along with focal areas of necrosis. On immunohistochemistry, tumor cells were diffusely and strongly positive for DOG1 and CD117. They were negative for smooth muscle actin, vimentin, S-100, and HMB-45. Based on these findings, a final diagnosis of the high-grade GIST epithelioid variant was made. It is crucial to make the correct preoperative diagnosis of GIST, since these patients may benefit from neoadjuvant imatinib, especially in case of large tumor size. [ABSTRACT FROM AUTHOR]