Challenges in Administering Salvage Therapy and Outcomes of Relapsed/Refractory Diffuse Large B-Cell Lymphoma Patients: A LMIC Real-World Study.

Standard therapy for patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (RR DLBCL) involves salvage chemotherapy followed by autologous hematopoietic stem cell transplant. However, information regarding the number of patients receiving salvage therapy and associated factors is not available from low/middle income countries (LMICs). All patients treated at our center with RR DLBCL from 2016 to 2021 were included in the study. Univariate and multivariate analyses was performed to find factors associated with the lack of receipt of salvage chemotherapy. Eighty-five patients were included in the study. Most patients had primary refractory disease (69.4%). Only 26 patients received standard salvage therapy, while the others (N = 59) received metronomic/palliative oral therapy. On univariate analysis, patients with an annual income below India's Gross National Income per capita (p = 0.014), an education level below Class XII (p = 0.025), Stage III/IV disease at relapse (p = 0.018) and CNS relapse (p = 0.027) were more likely to receive palliative therapy. Conversely, patients with a late relapse were more likely to receive salvage therapy (p = 0.001). On multivariate analysis, patients with Stage III/IV relapse (p = 0.030) and an education level less than Class XII (p = 0.012) were more likely to receive palliative therapy, while patients with a late relapse (p = 0.001) were more likely to receive salvage therapy. Patients who received salvage therapy had a longer Median OS than those who received palliative therapy (p < 0.001). Timing of relapse, stage at relapse and educational status of the patient are significant factors affecting access to effective therapy for patients with RR DLBCL in LMICs.

Adult Pulmonary Blastoma: A Case Report with Spectrum of Rare Manifestations.

Pulmonary blastoma (PB) is an exceedingly rare and aggressive malignant lung neoplasm that has distinct biphasic morphology. In this report, we document rare manifestations and molecular alterations in PB. A 59-year-old non-smoker female, presented with cough and hemoptysis for 4 months. The high-resolution computed tomography chest scan showed a 3.5x2.7 cm mass in the basal segment of the left lung. Positron emission tomography and computed tomography revealed a fluorodeoxyglucose avid lobulated mass in the superior segment of the lower lobe of the left lung. On core biopsy, the diagnosis of pleomorphic carcinoma in a background of adenocarcinoma was made. A definite diagnosis of pulmonary blastoma was established on the left lung lobectomy specimen based on morphological and immunohistochemical findings. Post-surgical biopsy from the scalp swelling showed metastatic deposits. On Next Generation Sequencing (NGS), in addition to conventional CTNNB1 gene mutation, new pathogenic MYCN and ATM gene mutations were detected. Post-chemotherapy, the patient was doing well after 10 months of close follow-up. PB exhibited rare associations in the form of non-smoker status, scalp metastasis, and MYCN and ATM gene mutations on NGS in addition to conventional CTNNB1 gene mutation. Large cohort studies are required to discover the incidence, significance and therapeutic implications of these co-existing pathogenic molecular alterations in PB.

The WHO system versus the Papanicolaou society of cytopathology system for reporting pancreaticobiliary cytology for risk stratification-which is better?

BACKGROUND: Recently, the World Health Organization (WHO) has proposed a reporting system for pancreaticobiliary cytopathology. We applied this classification for pancreatic lesion samples by fine needle aspiration (FNA) and compared the results to the previous classification of the Papanicolaou Society of Cytopathology (PSC) system for risk stratification. METHODS: The computerized database was searched for all pancreatic endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and transabdominal ultrasound-guided FNA (TUS-FNA) samples from 2016 to 2020 and cases were reassigned as per the PSC and the WHO diagnostic categories. Cases with follow-up, clinicoradiological, and/or histopathology were included in the study. The risk of malignancy (ROM) was calculated across all diagnostic categories based on clinical data, imaging data, and histopathology wherever available. RESULTS: There were a total of 625 pancreatic FNA. In 230 cases, follow-up information was available which included 116 EUS and 114 TUS-FNA samples. The ROM for PSC categories I-VI was 40%, 19.7%, 28.6%, 57.1%, 94.7%, and 97.9% and for the WHO categories (I-VII), it was 60%, 21.3%, and 35.7%, not representative, not applicable, 94.7% and 94.9%. The overall sensitivity and specificity of PSC was 68.2% and 96.2% when categories V and VI were taken as positive and 78.9% and 93.3% for WHO when categories VI and VII were taken as positive. CONCLUSIONS: Pancreatic FNA samples reported as per the WHO system showed better sensitivity as compared to the PSC system resulting in better risk stratification and consequently better patient management. The overall high specificity and moderate sensitivity reaffirm the utility of FNA in pancreatic lesions.

Cytology as the guiding light: Prompt cytomorphologic diagnosis of cystic metastases from a jejunal neuroendocrine tumor masquerading as hepatic abscesses.

Hepatic cystic lesions are commonly seen in radiology and can occur due to infective or neoplastic causes. It is imperative to determine the precise nature of these hepatic cysts owing to significant therapeutic and prognostic differences. Hepatic metastases from gastrointestinal neuroendocrine tumors (NETs) mostly present as solid hypervascular lesions. Cystic presentation of the metastatic NETs is extremely rare. A 64-year-old woman presented with an abdominal lump of 3 months duration and high-grade fever from the last 2 days. An ultrasound abdomen revealed multiple hypoechoic liver lesions suggestive of liver abscesses. An ultrasound-guided fine-needle aspiration (FNA) from the cystic liver lesions revealed a NET confirmed by immunocytochemistry. The Ki-67 index was 5%; hence, a final diagnosis of metastatic NET, grade 2, was given with advice to work up for localizing the primary tumor. Subsequently, a contrast-enhanced computerized tomography of the abdomen revealed a polypoidal lesion in the proximal jejunum, which showed intense expression on the whole-body DOTANOC scan (SUVmax-76.5), indicating it to be the likely primary tumor along with somatostatin receptor-expressing multiple lymph nodes and hypodense liver lesions. Thus, a final diagnosis of a jejunal NET with abdominal lymph node and liver metastases was made. The present report highlights the importance of FNA as a reliable modality in diagnosing metastatic NETs presenting as unusual cystic hepatic metastases masquerading as liver abscesses. Additionally, the cell block helps confirm the cytologic diagnosis and enables upfront tumor grading, thereby helping in prognostication and therapeutic decision-making.

Imaging CXCR4 receptors expression for staging multiple myeloma by using 68Ga-Pentixafor PET/CT: comparison with 18F-FDG PET/CT.

OBJECTIVES: 68Ga-Pentixafor positron emission tomography (PET) imaging targets CXCR4 expression which is overexpressed in multiple myeloma (MM). In this study, we evaluated the diagnostic utility of 68Ga-Pentixafor PET/CT for imaging CXCR4 expression in MM and compared results with 18F-fluorodeoxyglucose (18F-FDG) PET/CT. METHODS: 34 (21M; 13F; median age = 57.5 years) treatment naive multiple myeloma patients were recruited. All the patients underwent 18F-FDG PET/CT and 68Ga-Pentixafor PET/CT imaging. Freshly prepared 68Ga-Pentixafor (148-185 MBq) was injected intravenously and whole-body PET/CT (low-dose CT) was acquired at 1 h post-injection. The pattern of uptake (diffuse, focal or mixed) and the mean SUVmax value of all the lesions (when lesions were ≤5) or of the five most tracer avid lesions (when lesions was >5) were evaluated. Tumor to background ratio (TBRmax) was calculated for both the tracers. Durie Salmon plus staging (DSPS) was used for disease staging on PET and the results were compared with International staging system (ISS). RESULTS: 68Ga-Pentixafor PET/CT showed higher disease extent than seen on 18F-FDG PET/CT in 23/34 patients (68.0%), lesser disease extent in 2/34 (6%) and similar disease extent in 9/34 (26%) patients. Significantly (p < 0.001) higher TBRmax values (5.7; IQR 8.8) were observed on 68Ga-Pentixafor PET/CT as compared to 18F-FDG PET/CT values (2.9; IQR = 4.0). Both the techniques detected extramedullary lesions in six patients. On the other hand, 68Ga-Pentixafor detected medullary lesions in five, whereas, 18F-FDG PET in three patients. Further, only 68Ga-Pentixafor TBRmax correlated significantly (ρ = 0.421; 0.013) with bone marrow plasma cell percentage. 68Ga-Pentixafor PET upstaged more number (9/29) of patients as compared to (4/29) 18F-FDG PET imaging. On the other hand, 18F-FDG PET down-staged 9/29, whereas 68Ga-Pentixafor PET downstaged only 3/29 patients. CONCLUSION: 68Ga-Pentixafor PET/CT evaluated the whole-body disease burden of CXCR4 receptors non-invasively which is not possible by tissue sampling methods. This novel PET tracer has also implication for disease staging. Dual 68Ga-Pentixafor/18F-FDG PET/CT imaging may help in determining the tumor heterogeneity in MM. ADVANCES IN KNOWLEDGE: This CXCR4 targeting PET tracer has a promising role in the development of CXCR4 targeting theranostics and also for response assessment to these therapies including the conventional treatment.

Successful Use of High Dose Methotrexate in Treatment of Primary CNS Lymphoma Patients Without Access to Serum Methotrexate Levels Monitoring: Challenges and Outcome.

AIMS AND OBJECTIVES: High dose methotrexate (HDMTx) based chemotherapy forms the backbone of therapy for patients with Primary Central Nervous system Lymphoma (PCNSL). However, delivering HDMTx in resource constrained settings, especially without therapeutic drug monitoring, is difficult. We share our experience of treatment of patients with PCNSL at our center over a 10-year period with local adaptations made to deliver HDMTx. MATERIALS AND METHODS: We retrospectively analysed the case records of patients diagnosed with a PCNSL over the course of 10 years from 2010 to 2020. RESULTS: Fifty-five patients received therapy for newly diagnosed PCNSL. Thirty-six patients received Modified De-Angelis protocol ± Rituximab with curative intent. Fourteen of these patients were unable to complete the protocol with the most common cause being development of methotrexate toxicity. Patients unable to complete the designated 5 cycles of HDMTx had a poorer PS and higher probability of having a high IELSG score at baseline. Nineteen patients were given non HDMTx based therapy either due to advanced age or poor performance status. Twenty-nine patients (52.7%) were able to achieve a complete response. The most common cause of mortality was relapse/progressive disease. The Median EFS and OS of the cohort was 29 months and 40 months respectively. CONCLUSION: All attempts should be made to have therapeutic drug level monitoring for administration of HDMTX based therapy for the patients with PCNSL, more so in patients who have poor performance status and a high IELSG score. If it is imperative to give HDMTx without access to TDM facility then a possible risk of higher toxicity should be explained to all patients, beforehand.

Bendamustine in combination with ifosfamide, etoposide, and vinorelbine (VIBE) is an effective salvage regimen for heavily pre-treated patients with relapsed or refractory Hodgkin lymphoma: a single-center experience.

BACKGROUND: This study evaluated the outcomes of patients with refractory/relapsed Hodgkin lymphoma (RRHL) treated with a bendamustine-based regimen in combination with ifosfamide, etoposide, and vinorelbine (VIBE). METHODS: Consecutive RRHL patients who were treated with the VIBE regimen were identified and studied for clinicopathologic characteristics, response to VIBE regimen, event-free survival (EFS), and feasibility of an autologous stem-cell transplant (autoSCT). RESULTS: In total, 24 patients received the VIBE regimen, and a median of 3 cycles were administered. In this cohort, 80% of the patients had received ≥2 prior lines of therapy. The overall and complete response rates with VIBE were 79% and 42%, respectively. After a median follow-up (following VIBE regimen) of 14 months (range, 3‒76), the 3-year EFS and OS were 46% and 74%, respectively. Of the eligible patients, 92% underwent successful AutoSCT. The mean CD34+ cell count in the autograft was 5.5×106/kg (SD 2.07). Neutropenia was the commonest hematologic toxicity and it was observed in 42% of the patients. However, only 9% of the patients developed grade III/IV febrile neutropenia. Chemotherapy-induced nausea and vomiting were the second most common grade III/IV toxicities in our cohort of patients. CONCLUSION: In this retrospective analysis, the combination regimen, VIBE, has shown good efficacy in heavily pre-treated patients with RRHL without compromising stem cell collection. These encouraging results provide a rationale for further development of this regimen.

Locally advanced gallbladder cancer: a review of the criteria and role of imaging.

Gallbladder carcinoma (GBC) is among one of the gastrointestinal malignancies with extremely dismal prognosis. This is due to the advanced stage at presentation. Majority of the patients with GBC are not considered candidates for surgery because of the locally advanced disease or metastases. However, with the accumulating evidence regarding the role of neoadjuvant chemotherapy, there is a need to correctly identify a subset of patients with locally advanced GBC who will benefit maximally from neoadjuvant chemotherapy and will be successfully downstaged to receive curative (R0) surgery. In this context, there is a lack of consensus and different groups have resorted to criteria for locally advanced disease eligible for neoadjuvant chemotherapy based on personal or institutional experiences. Imaging plays a critical role in the evaluation of patients with GBC as it helps stratify patients into resectable and unresectable. Imaging also has the potential to identify patients with locally advanced GBC and hence facilitate neoadjuvant chemotherapy and improve outcomes. In this review, we evaluate the various criteria for locally advanced GBC and the role of imaging in this scenario.

Intraoperative transesophageal echocardiography: A complement to 18F-fluorodeoxyglucose positron emission tomography-computed tomography in localizing pacemaker lead endocarditis.

Lead endocarditis (LE) is a serious complication of permanent trans-venous pacing. Localizing LE may be challenging with conventional imaging modalities. 2-deoxy-2-[fluorine-18] fluoro-D-glucose positron emission tomography-computed tomography (FDG PET/CT) has recently emerged as a promising tool in the diagnosis of LE particularly in cases with normal echocardiographic imaging findings and/or negative blood culture. However, this technique is associated with some drawbacks. Knowledge of these drawbacks and correlating its limitations with other imaging modality is essential for the echocardiographer while evaluating such patient. We report a case where transesophageal echocardiography was complementary to FDG PET/CT in the diagnosis and localization of vegetation over pacemaker leads during intraoperative period.

68Ga-DOTA-Exendin PET-MRI Fusion Imaging in a Case of Insulinoma.

Persistent hyperinsulinemic hypoglycemia in adults is most commonly caused by insulinomas, which pose a diagnostic challenge to physicians, surgeons, and radiologists and require multimodality imaging for precise localization and staging. PET tracers such as F-FDOPA and glucagon-like peptide 1 receptor analogs have been used for imaging insulinomas. Glucagon-like peptide 1 receptor analogs have recently shown promising results in preoperative localization of these tumors, as all insulinomas express glucagon-like peptide 1 receptors. Ga-DOTA-Exendin PET and MRI done in the present case helped in precise localization and management of the culprit lesion, whereas contrast-enhanced CT and F-FDOPA PET failed to do so.

Role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in restaging and prognosis of recurrent melanoma after curative surgery.

Malignant melanoma is a highly aggressive tumor and surgical resection is the primary treatment. However, the chances of recurrence are quite high despite complete resection. The aim of study was to evaluate the 18F-fluorodeoxyglucose(18F-FDG) positron emission tomography-computed tomography (PET/CT) in detection of recurrent melanoma after curative surgery and its prognostic value. Fifty-four melanoma patients (32 women) with prior primary lesion resection were evaluated with 18F-FDG PET/CT for clinically suspicious recurrent disease. The diagnostic accuracy of 18F-FDG PET/CT (visual interpretation as well as semi-quantitative parameter) was determined on the basis of subsequent imaging and clinical follow-up. Melanoma-specific survival and risk of progression (hazard ratio [HR]) were assessed using Kaplan-Meier method and Cox regression analysis. 18F-FDG PET/CT detected recurrent diseases in 36 (66%) patients including distant metastases in 13 patients and second synchronous malignancy in 2 patients. Overall, the sensitivity, specificity, positive predictive value, and negative predictive value of 18F-FDG PET/CT were 91.2%, 80.0%, 88.6%, and 84.2%, respectively, with area under the curve of 0.86 (95% confidence interval: 0.74-0.97; P < 0.05). Positive 18F-FDG PET/CT study was associated with a significantly shorter overall survival than negative study (30.8 ± 4.6 vs. 64.5 ± 6.9 months, P < 0.05). Apart from positive 18F-FDG PET/CT scan, maximum standardized uptake value (SUVmax) >2.7 and combination of both were independently associated with an increased risk of disease progression (HR = 7.72, 21.58, and 11.37, respectively; P < 0.05). 18F-FDG PET/CT showed enhanced diagnostic performance in patients with suspicious recurrent malignant melanoma leading to appropriate management. FDG positivity along with SUVmax >2.7 provides important prognostic value in predicting the survival outcomes and assessing the risk of disease progression.

An uncommon case of gall bladder mass: gall bladder tuberculosis.

Gall bladder tuberculosis (TB) is a rare entity and differentiation of gall bladder TB from gall bladder malignancy is difficult. We hereby present an unusual case of incidental diagnosis of gall bladder TB during the evaluation of a gall bladder with suspicion of gall bladder cancer in a 49-year-old woman. The diagnosis of gall bladder TB was made with fine needle aspiration cytology (FNAC) from the gall bladder mass as the disease was found unresectable after cross-sectional imaging. Even with the advancement of cross-sectional imaging, the differentiation of gall bladder TB from gall bladder malignancy is not possible without tissue diagnosis.

18F-FDG-Labeled Autologous Leukocyte PET-CT in a Patient With Aortic Valve-Tube Graft Infection After Bentall Procedure.

Infection of aortic valve-tube graft, although rare, is associated with high morbidity and mortality. Early identification of site and extent of infection is not only challenging but also crucial for adequate patient management and prognostication of disease. Combined clinical, laboratory investigation and imaging modalities assist in the identification of aortic valve graft infection. Molecular imaging techniques like PET/CT using F-FDG and F-FDG-labeled autologous leukocytes (LALs) have improved the sensitivity for detection of infection, resulting in better outcome for these patients. F-FDG-labeled autologous leukocyte PET/CT in our patient after Bentall procedure accurately localized the site and extent of infection.

Diagnostic and prognostic value of 18F-FDG PET/CT imaging in suspected recurrence of male breast cancer.

PURPOSE: Male breast cancer (MBC) is a rare malignancy, with recurrence being one of the main adverse predictors for prognosis. The aim of the study was to evaluate the diagnostic and predictive value of fluorine-18-fluorodeoxyglucose (F-FDG) PET/CT in the setting of suspected recurrence of MBC. PATIENTS AND METHODS: Retrospective analysis of PET/CT findings was performed in 23 previously treated, histologically proven patients with MBC (mean age: 59.3±10.9 years; range: 36-79 years) with suspected recurrence. Kaplan-Meier disease-specific survival analysis was made with respect to histological, hormonal profile as well as PET/CT findings. RESULTS: Of the 23 patients, 19 (82.6%) showed recurrence. Recurrence at primary site with/without regional/distant site recurrence was seen in 12 (52.2%) patients. Only metastatic recurrence without primary site was seen in seven (30.4%) patients. Bone was the most common site of distant metastasis (14/23) followed by lungs (9/23), liver (4/23), brain (2/23), and adrenal (1/23). No recurrence (regional/distant) was noted in 4/23 (17.3%) patients; however, three of them had F-FDG-avid soft tissue lesions in esophagus, rectum and tongue, correspondingly, confirmed as second primaries with histopathology. Disease-specific survival analysis yielded nodal (P=0.01) as well as distant metastases (P=0.02) as the main survival predictors on PET/CT. Lung (P=0.001), followed by liver (P=0.009), and skeletal (P=0.01) metastases were the most adverse survival predictive factors. CONCLUSION: F-FDG PET/CT showed good diagnostic and prognostic utility in recurrent MBC. It was better than bone scan in evaluation of skeletal metastases. Most importantly, F-FDG PET/CT helped in early detection of second malignancy and their clinical management in studied patients.

Incidental Detection of Plasma Cell Neoplasm on 18F-Choline PET/CT Imaging.

F-Fluorocholine is a relatively new, extremely versatile radiotracer for detecting proliferative or mitogenic activity. Its diagnostic potential has been explored in cancers of the prostate, liver, esophagus, breast, brain, and lung, as well as lymphoma, sarcoma, melanoma, and parathyroid adenomas. The authors present a case where fluorocholine PET/CT performed for characterizing a space-occupying lesion in the brain revealed intensely tracer-avid skull lesions with intracranial soft tissue component and multiple other skeletal lesions. Fine-needle aspiration cytology from the skull and chest wall lesions confirmed the diagnosis of plasma cell neoplasm.

Nonspecific Uptake of 68Ga-Prostate-Specific Membrane Antigen in Diseases other than Prostate Malignancy on Positron Emission Tomography/Computed Tomography Imaging: A Pictorial Assay and Review of Literature.

68Ga-labeled prostate-specific membrane antigen (PSMA) ligand positron emission tomography/computed tomography imaging (PET/CT) is a rapidly evolving imaging modality for prostate cancer. Many studies have proved its superiority in staging, restaging, and detecting the recurrent prostate cancer. However, case reports describing the incidental tracer uptake in benign and nonprostatic malignancies are also reported in the literature, thus questioning the specificity of the tracer. This pictorial assay illustrates the nonspecific tracer uptake encountered during PSMA PET/CT imaging, knowledge of which can increase the confidence of interpreting physicians and may also open a new path for peptide receptor radionuclide therapy in nonprostatic malignancies.