Tumor-associated macrophages: A sentinel of innate immune system in tumor microenvironment gone haywire.

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.

Bilateral primary ovarian Ewing sarcoma recurring as left submandibular lymphadenopathy diagnosed on cytology.

Ewing sarcoma (ES) is a highly malignant and aggressive small round-cell tumor originating from primitive neuroepithelium and mesenchymal stem cells. It is usually seen in children and adolescents with a male predilection and a preponderance to occur in long bones. Although skeletal/soft tissue ES is encountered in clinical practice, primary ES of the genital tract, particularly bilateral primary ovarian ES, is highly uncommon, with only a handful of cases reported worldwide. Ovarian ES is occasionally reported to involve para-aortic and pelvic lymph nodes in advanced stages. Still, cervical lymph node metastasis from ovarian ES is an infrequent clinical occurrence and, when present, indicates a worse prognosis. Here, we present an intriguing case of bilateral peripheral primary ovarian ES in an adult female, recurring as metastasis in the left submandibular lymph node. This case underlines the importance of keeping metastasis from ES as a possible differential while diagnosing metastatic small round cell tumors in peripheral lymph nodes. It also highlights the usefulness of a minimally invasive diagnostic modality of fine needle aspiration cytology and cell block preparation with applied ancillary techniques of immunohistochemistry and confirmatory molecular testing by fluorescence in-situ hybridization (FISH), for an accurate and quick diagnosis of such entities. The cytological diagnosis of our patient helped in the prompt and early initiation of chemotherapy without requiring any invasive procedure.

ChatGPT as an aid for pathological diagnosis of cancer.

Diagnostic workup of cancer patients is highly reliant on the science of pathology using cytopathology, histopathology, and other ancillary techniques like immunohistochemistry and molecular cytogenetics. Data processing and learning by means of artificial intelligence (AI) has become a spearhead for the advancement of medicine, with pathology and laboratory medicine being no exceptions. ChatGPT, an artificial intelligence (AI)-based chatbot, that was recently launched by OpenAI, is currently a talk of the town, and its role in cancer diagnosis is also being explored meticulously. Pathology workflow by integration of digital slides, implementation of advanced algorithms, and computer-aided diagnostic techniques extend the frontiers of the pathologist's view beyond a microscopic slide and enables effective integration, assimilation, and utilization of knowledge that is beyond human limits and boundaries. Despite of it's numerous advantages in the pathological diagnosis of cancer, it comes with several challenges like integration of digital slides with input language parameters, problems of bias, and legal issues which have to be addressed and worked up soon so that we as a pathologists diagnosing malignancies are on the same band wagon and don't miss the train.

Bilateral primary ovarian Ewing sarcoma recurring as left submandibular lymphadenopathy diagnosed on cytology

ABSTRACT Ewing sarcoma (ES) is a highly malignant and aggressive small round-cell tumor originating from primitive neuroepithelium and mesenchymal stem cells. It is usually seen in children and adolescents with a male predilection and a preponderance to occur in long bones. Although skeletal/soft tissue ES is encountered in clinical practice, primary ES of the genital tract, particularly bilateral primary ovarian ES, is highly uncommon, with only a handful of cases reported worldwide. Ovarian ES is occasionally reported to involve para-aortic and pelvic lymph nodes in advanced stages. Still, cervical lymph node metastasis from ovarian ES is an infrequent clinical occurrence and, when present, indicates a worse prognosis. Here, we present an intriguing case of bilateral peripheral primary ovarian ES in an adult female, recurring as metastasis in the left submandibular lymph node. This case underlines the importance of keeping metastasis from ES as a possible differential while diagnosing metastatic small round cell tumors in peripheral lymph nodes. It also highlights the usefulness of a minimally invasive diagnostic modality of fine needle aspiration cytology and cell block preparation with applied ancillary techniques of immunohistochemistry and confirmatory molecular testing by fluorescence in-situ hybridization (FISH), for an accurate and quick diagnosis of such entities. The cytological diagnosis of our patient helped in the prompt and early initiation of chemotherapy without requiring any invasive procedure.

Prognostic evaluation of cancer associated fibrosis and tumor budding in colorectal cancer.

Colorectal carcinoma (CRC) is the second most common cancer and third leading cause of cancer-related deaths worldwide. Although the staging system provides a standardized guidance in treatment regimens, the clinical outcome in patients with colon cancer at the same TNM stage may vary dramatically. Thus, for better predictive accuracy, further prognostic and/or predictive markers are required. Patients who underwent curative surgery for colorectal cancer in past 3 years at a tertiary care hospital were retrospectively included in this cohort study to evaluate the prognostic indicators, tumor-stroma ratio (TSR) and tumor budding (TB) on histopathological sections and correlated them with pTNM staging, histopathological grading, tumor size, and lymphovascular and perineural invasion in patients with colo-rectal cancer. TB was strongly associated with advanced stage of the disease along with lympho-vascular and peri-neural invasion and it can be used as an independent adverse prognostic factor. TSR showed a better sensitivity, specificity, PPV and NPV as compared to TB in patients having poorly differentiated adenocarcinoma than those with moderately or well differentiated.

Pituitary tuberculoma with panhypopituitarism masquerading as a pituitary adenoma.

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.