AI powered quantification of nuclear morphology in cancers enables prediction of genome instability and prognosis.

While alterations in nucleus size, shape, and color are ubiquitous in cancer, comprehensive quantification of nuclear morphology across a whole-slide histologic image remains a challenge. Here, we describe the development of a pan-tissue, deep learning-based digital pathology pipeline for exhaustive nucleus detection, segmentation, and classification and the utility of this pipeline for nuclear morphologic biomarker discovery. Manually-collected nucleus annotations were used to train an object detection and segmentation model for identifying nuclei, which was deployed to segment nuclei in H&E-stained slides from the BRCA, LUAD, and PRAD TCGA cohorts. Interpretable features describing the shape, size, color, and texture of each nucleus were extracted from segmented nuclei and compared to measurements of genomic instability, gene expression, and prognosis. The nuclear segmentation and classification model trained herein performed comparably to previously reported models. Features extracted from the model revealed differences sufficient to distinguish between BRCA, LUAD, and PRAD. Furthermore, cancer cell nuclear area was associated with increased aneuploidy score and homologous recombination deficiency. In BRCA, increased fibroblast nuclear area was indicative of poor progression-free and overall survival and was associated with gene expression signatures related to extracellular matrix remodeling and anti-tumor immunity. Thus, we developed a powerful pan-tissue approach for nucleus segmentation and featurization, enabling the construction of predictive models and the identification of features linking nuclear morphology with clinically-relevant prognostic biomarkers across multiple cancer types.

Treatment Complications of Head and Neck Cancers and Rehabilitation Measures: A Narrative Review.

Head and neck cancers (HNCs) are malignant tumors mainly from squamous cells in the head and neck tissues. Treatment involves a multidisciplinary approach with surgery, radiotherapy, and chemotherapy. However, the long-term prognosis for patients with advanced-stage tumors is guarded, with a median survival time of approximately 24 months. HNC patients have very high rates of depression and anxiety and the highest suicide rate among all cancers due to the intense and challenging nature of the treatment, underscoring the importance of our collective efforts. Rehabilitation success depends on various factors, including tumor, patient, and treatment-related factors. Patients may require post-treatment oral rehabilitation measures, including implants, obturators, and flexible dentures. These measures are crucial, but they often need to be more utilized. Patients may face challenges in maintaining oral hygiene and managing mucositis. Additionally, it is essential to address other intricacies such as trismus, xerostomia, gustatory dysfunctions, neuropathy, speech impairments, and psychological disturbances. Unfortunately, there is little literature on post-treatment rehabilitative measures. Despite its crucial role in improving patients' quality of life, rehabilitation often receives inadequate attention compared to treatment. Our narrative review, which covers various factors that affect rehabilitation, including oral rehabilitation measures and post-treatment complications, is anticipated to deliver practical insights to professionals and inspire positive changes in their regular practice.

Diagnostic and therapeutic challenges in a recurrent endometrial carcinoma in lung, 15 years after primary treatment.

Endometrial carcinoma (EC) is the sixth most common cancer in females. Most ECs are detected in stage 1 and have a 5-year survival rate of more than 90%. Recurrence rates are highest within 5 years after treatment and are exceptionally rare after 10 years. Here, we describe a woman in her late 70s with endometrial cancer who was treated in 2008 and was diagnosed with a relapse in her left lung in 2023. Due to her advanced age and comorbidities, she was deemed inoperable. However, she received sequential chemotherapy and radiotherapy with a good partial response. She has now been started on hormonal therapy with an alternate megestrol and tamoxifen regime. There is a lack of follow-up imaging guidelines to detect late relapse, a dilemma in preferred treatment sequencing at relapse and an enigma in selecting chemotherapy or hormonal therapy.

Evaluation of Different Regimens of Palliative Radiation Therapy for Symptomatic Bone Metastases: An Audit From a Tertiary Care Hospital in Jharkhand, India.

Background This study aimed to assess the efficacy of different radiation therapy regimens in treating patients with symptomatic bone metastases. Methodology A retrospective study was conducted by assigning patients with symptomatic bone metastases from different primary cancers into three groups, namely, Arms A, B, and C. The radiation dose delivered in each arm was as follows: 8 Gray (Gy) in a single fraction for Arm A, 20 Gy in five fractions at the rate of 4 Gy per fraction for Arm B, and 30 Gy in 10 fractions at the rate of 3 Gy per fraction for Arm C. Each arm consisted of 15 patients. A comparison was conducted across all three arms to evaluate pain relief based on the Visual Analog Scale (VAS), performance score improvement based on the Eastern Cooperative Oncology Group (ECOG), and analgesic requirement based on the World Health Organization (WHO) step ladder at one week, one month, and three months. Results The pain relief was measured using the VAS in three different arms, i.e., Arm A, B, and C. After one week, the pain relief was 66.67%, 60%, and 60%, respectively. After one month, it was 73.33% in all three arms. At three months, it was 80%, 86.67%, and 86.67%, respectively. The study also measured the improvement in the ECOG performance score. The improvement in all three arms was 60% after one week and 66.67% in Arm A and 73.33% in Arms B and C after one month. After three months, the improvement was 73.33%, 80%, and 80% in Arms A, B, and C, respectively. The decrease in analgesic usage was also measured in all three arms. After one week, it was 60% in all three arms. After one month, it was 66.67%, 73.33%, and 73.33% in Arms A, B, and C, respectively. At three months, it was 73.33%, 80%, and 80% in Arms A, B, and C, respectively. No significant statistical difference was found between the three arms. Conclusions The efficacy of a single 8 Gy arm was almost equivalent to that of other arms of multifractionated regimens in terms of improvement in pain and performance score and decreased use of analgesics for a short duration of follow-up. For high-volume cancer centers and patients with economic constraints, a single-fraction regime provides effective palliation for painful bone metastases.

A Rare Case of Neuroendocrine Prostate Cancer Detected on 68Ga - DOTANOC Positron Emission Tomography/Computed Tomography (PET/CT).

Prostate cancer is one of the most common malignancies affecting elderly men worldwide and the fifth leading cause of cancer death in men. Prostate cancer includes many histological variants with the prostatic acinar adenocarcinoma variant accounting for the majority of the diagnosed cases. Other less common histological variants are broadly classified as non-acinar carcinomas. One of the non-acinar carcinoma variants is neuroendocrine prostate cancer (NEPC). NEPC can emerge as a mechanism of treatment resistance in castration-resistant conventional prostate cancer and can also rarely be seen as a primary histological form at the time of initial diagnosis. Like other non-acinar carcinoma variants of prostate cancer, NEPC is also an aggressive variant with associated poor prognosis. Neuroendocrine tumors (NETs) are characterized by the expression of somatostatin receptors (SSTRs). Positron emission tomography/computed tomography (PET/CT) using radiolabeled somatostatin analogs like DOTANOC have been used to detect and stage these NETs. These radiolabeled somatostatin analogs also provide the option of treatment of these tumors and have been used in peptide receptor radionuclide therapy of these tumors. NEPC being a neuroendocrine malignancy also expresses SSTRs and hence can be detected with PET/CT radiotracers like 68Gallium-labeled somatostatin analogs. We here report a case of metastatic treatment-emergent NEPC detected on 68Ga - DOTANOC PET/CT.

Association Between Synchronous Occurrence of Multiple Myeloma and Carcinoma Prostate: Literature Analysis in the Context of a Case Report.

Carcinoma of the prostate is the second most common cancer in males, while multiple myeloma is the 17th most common cancer. The synchronous diagnosis of multiple myeloma and carcinoma of the prostate is a sporadic phenomenon with scarce published literature and a diagnostic and therapeutic dilemma. Here, we present a case of synchronous diagnosis of IgG and lambda subtypes of multiple myeloma with multiple lytic lesions, the revised international staging system (R-ISS 2), and non-metastatic acinar adenocarcinoma prostate, a very high-risk category. The patient received 25 weekly doses of cyclophosphamide, bortezomib, and dexamethasone (CyBorD)-based chemotherapy for myeloma and androgen deprivation therapy with injection leuprolide for prostate cancer. After reasonable disease control, the patient underwent an autologous stem cell transplant for multiple myeloma with melphalan at 140 mg/m2 and was offered definitive radiation therapy for prostate cancer. The potential association between carcinoma of the prostate and multiple myeloma has been hypothesized because of similarities in the tumor microenvironment. There are possible common biological pathways leading to co-stimulatory mechanisms, like interleukin-2 (IL-2), insulin-like growth factor 1 (IGF-1), stromal cell-derived factor 1 (SDF-1), and vascular endothelial growth factor (VEGF). However, they are not proven and warrant further research. This case highlights key areas of diagnosis and management of this sporadic occurrence, along with literature analysis and the need for further research, and is likely to be beneficial for clinicians in decision-making in future cases.

Extragonadal Nongestational Choriocarcinoma With a Widespread Metastasis in a Young Female: A Case Report and Literature Analysis With a Focus on Unmet Needs.

Choriocarcinoma is a highly aggressive malignant tumor that occurs due to the formation of an abnormal trophoblast. Choriocarcinoma is classified into gestational (GC) and nongestational (NGC) subtypes. The majority of nongestational diseases are limited to ovaries. Extragonadal NGC is a sporadic occurrence and a diagnostic and therapeutic dilemma. Here, we present a young 24-year-old female who presented with a widespread metastatic disease to the brain, bilateral kidneys, lungs, liver, pancreas, and small bowel. She was diagnosed with extragonadal NGC, probably originating from her kidneys. She responded poorly to standard first-, second-, and third-line chemotherapies. Detailed literature analysis with various aspects of pathogenesis, diagnostic criteria, clinical presentation, and treatment options are discussed. There is an unmet need for further research and consensus on many aspects of this rare disease.

Embolization of a Fractured Peripherally Inserted Central Catheter to Pulmonary Arteries: A Sporadic Life-Threatening Phenomenon.

The peripherally inserted central catheter (PICC) is a non-tunneled central venous catheter placed in the upper limb venous system, mainly in the basilic vein, and the tip terminates in the superior vena cava (SVC). A PICC is a preferred modality of central venous access in oncology, as it is associated with minimal discomfort and can be kept in situ for up to one year. Despite multiple advantages, it is also associated with complications. Fracture and migration are rare but potentially serious complications that can lead to arrhythmias, cardiac perforation, cardiac tamponade, pulmonary embolism, and sepsis. The migrated PICC fragment can be retrieved using percutaneous techniques, which have a high success rate of excess, with minimum complications. In our patient of adenocarcinoma gastroesophageal junction, the fractured and migrated PICC to pulmonary arteries was retrieved using the balloon catheter method. With more and more cancer patients using PICCs for chemotherapy administration, healthcare workers must be aware of the standard and sporadic complications of PICCs. Care of the PICC is crucial, and any lapse may lead to fracture and embolization, which is a potentially life-threatening complication. This case highlights the importance of healthcare persons being aware of the possibility of catheter embolization and methods to prevent and mitigate this phenomenon.

Synchronous Adenocarcinoma Stomach With Marginal Zone Lymphoma: A Sporadic Occurrence and Review of Literature.

Synchronous adenocarcinoma of the stomach with lymphoma is extremely rare. We report a case of a 65-year-old male patient with synchronous adenocarcinoma of the stomach with nodal marginal zone lymphoma. Initial endoscopic biopsy suggested invasive moderately differentiated adenocarcinoma and a locoregional disease, per contrast-enhanced computed tomography (CECT) scans. The patient was started on neo-adjuvant chemotherapy with the 5FU, leucovorin, oxaliplatin, docetaxel (FLOT) regime and, after response evaluation, underwent radical gastrectomy. Histopathology and immunohistochemistry suggested synchronous adenocarcinoma of the stomach with marginal zone lymphoma in perigastric lymph nodes. This case is probably the first such synchronous malignancy case reported from India. The prognosis of multiple primary malignancies is usually poor because no standard guidelines are available regarding optimum treatment and sequencing of available treatment modalities. The frequency of synchronous primary cancers has been increasing in recent years, probably due to better diagnostic modalities, and second primary in patients with cancer should be considered as one of the differential diagnoses.

Clinicopathological Profile of Breast Cancer at a Tertiary Cancer Center in Jharkhand, India: A Descriptive Cohort Study.

Introduction Breast cancer is the most common cancer in females worldwide including Indian urban areas. There is no concrete data on breast cancer epidemiology from the state of Jharkhand, India. Materials and methods The present study is a retrospectively conducted descriptive cohort study. A total of 759 patients were selected from the database from 2012 to 2022. The parameters taken for the study were age, sex, stage at the time of presentation, histological type, estrogen receptor (ER) status, progesterone receptor (PR) status, human epidermal growth receptor 2 (HER2) neu status (HER2/neu), site of metastasis for stage 4 diseases, parity, and significant family history. Results The median age for patients was 49 years (range: 19-91 years), with a clustering of 74.83% of cases between 31 and 60 years of age. Most of the patients were in stage III, with 365 (48.08%) cases. Bone was the commonest site of metastasis and was found in 41.25% of total cases. The total number of hormone receptor-positive patients was 384 (56.2%), the number of HER2/neu positive patients was 210 (30.7%), and triple-negative breast cancer was found in 184 cases (26.93%). Conclusion The pattern found in our Jharkhand patients was very much similar to other Indian studies with slightly more clustering of younger cases. The cases in India are almost a decade younger than the Western population and the same was replicated in our study. This is one of the largest studies on breast cancer profile and epidemiology from the eastern part of India. Most of our patients presented late, leading to a higher number of locally advanced (stage III) and metastatic (stage IV) cases. More awareness is required at the population level, including strict implementation of a robust screening program by our government, for improving the overall outcome.

Cutaneous Metastasis of Carcinoma Buccal Mucosa: A Rare Presentation.

Cutaneous metastasis (CM) of head-and-neck squamous cell carcinoma is rarely reported. Here, we report a case of a 78-year-old male who had already had a surgically treated case of carcinoma of the right buccal mucosa one and a half months back but presented with a near local site recurrence and subsequently developed distant skin metastases to the lower neck and upper trunk during treatment. Local site recurrence was confirmed with a biopsy, but benign-looking lesions in the lower neck and upper trunk were developed during the last week of treatment, which later on kept growing in size and after the biopsy came positive for malignancy. Although there was a complete response at the recurred site of malignancy, there was a progression of disease at the initially benign-looking lesion in the lower neck and upper trunk, which later on was proven to be cutaneous malignancy on histopathology. This case has cemented the fact that the chance of the presence of occult skin metastasis at the time of diagnosis in primary or recurrent malignancies. Thus, tissue biopsy should be done with a high index of suspicion for cutaneous malignancy associated with head and neck cancers.

A Rare Case of Chondrosarcoma With Metastasis to the Oral Cavity.

Chondrosarcomas with metastases to oral cavities are extremely rare. To the best of our knowledge, only six cases of chondrosarcoma with metastases to the oral cavity, maxilla, and/or mandible have been reported in the English-language literature. The last such case was reported three decades earlier; none of the reported cases were from India. We present the case of an Indian patient with chondrosarcoma in the knee region, who was treated with surgical excision in 2013. However, he experienced a recurrence in 2019, developed upper gingival metastasis in 2020, and succumbed within two months of this unique presentation. Oral metastatic lesions have a wide differential diagnosis, and awareness of this rare presentation can help clinicians maintain an index of suspicion for an underlying metastatic malignancy. Our experience emphasizes the importance of detailed history-taking, clinical examination, and consideration of metastases as a differential diagnosis, even if there is no reported history of malignancy. Such lesions may also be the first sign of an occult primary tumor, which will require prompt investigation for early diagnosis and treatment.

A Rare Case of Metastases to Paranasal Sinus From Colonic Adenocarcinoma.

Metastases of malignant tumors to the nasal cavity and paranasal sinuses are very rare. Metastases to these locations are usually solitary and produce similar symptoms to those of a primary sinonasal tumor. Pain, nasal obstruction, and epistaxis are the most common symptoms. Although any malignancy could potentially lead to metastasis to the paranasal sinuses, colo-rectal malignancy metastasizes to this site is rare. We report a case of metastatic adenocarcinoma of colorectal origin to the paranasal sinuses in a 55-year-old female who was initially diagnosed with adenocarcinoma of the colon with lung and liver metastasis. She subsequently developed metastasis to left ethmoidal and sphenoidal sinuses during treatment. A histologic study of the surgical specimen from the sinonasal cavity demonstrated a tumor identical to the patient's prior primary tumor of the colon. The sinonasal neoplastic tissue showed marked positivity for carcinoembryonic antigen and expressed cytokeratin 20, which differentiates metastatic colonic adenocarcinoma from primary intestinal-type adenocarcinoma (ITAC). She received palliative radiation therapy but died three months after the diagnosis. These subsets of patients have a poor prognosis. In the majority of patients, palliative therapy is the only possible treatment option. Nevertheless, whenever possible, surgical excision either alone or combined with radiotherapy may be useful for palliation of symptoms and, rarely, to achieve prolonged survival.

Human-interpretable image features derived from densely mapped cancer pathology slides predict diverse molecular phenotypes.

Computational methods have made substantial progress in improving the accuracy and throughput of pathology workflows for diagnostic, prognostic, and genomic prediction. Still, lack of interpretability remains a significant barrier to clinical integration. We present an approach for predicting clinically-relevant molecular phenotypes from whole-slide histopathology images using human-interpretable image features (HIFs). Our method leverages >1.6 million annotations from board-certified pathologists across >5700 samples to train deep learning models for cell and tissue classification that can exhaustively map whole-slide images at two and four micron-resolution. Cell- and tissue-type model outputs are combined into 607 HIFs that quantify specific and biologically-relevant characteristics across five cancer types. We demonstrate that these HIFs correlate with well-known markers of the tumor microenvironment and can predict diverse molecular signatures (AUROC 0.601-0.864), including expression of four immune checkpoint proteins and homologous recombination deficiency, with performance comparable to 'black-box' methods. Our HIF-based approach provides a comprehensive, quantitative, and interpretable window into the composition and spatial architecture of the tumor microenvironment.