Double trouble: insights from a rare case of extranodal composite lymphoma in an elderly man, with comprehensive literature review.

Composite lymphoma (CL) is a rare cancer characterized by the concurrent occurrence of more than one type of lymphoma within the same organ or tissue in an individual. Its occurrence at extranodal sites is exceptional, with only a few cases documented in the literature. A 62-year-old gentleman presented with dystonia, dysphagia, and irregular enlargement of the right tonsil for the last three months. Based on a clinical suspicion of tonsillar malignancy, tonsillectomy was done. The histopathologic examination revealed effacement of the architecture by large irregular lymphoid nodules with interfollicular expansion. The nodules showed sheets of small atypical lymphoid cells, while the interfollicular areas showed large atypical lymphoid cells with scattered typical binucleate Reed-Sternberg cells. Immunohistochemistry confirmed mantle cell lymphoma (MCL) in the nodules and classical HL (cHL) in the interfollicular areas. Based on these features, a diagnosis of composite MCL with cHL was rendered. He was treated with bendamustine and rituximab chemotherapy and remained in complete remission for five years when he presented with significant right-sided neck swelling. Percutaneous fine needle aspiration and subsequent flow cytometry confirmed a relapse of the MCL component of the CL. The index report documents an exceptional case of CL, comprising MCL and cHL, presenting at an uncommon extranodal site. In addition, it also emphasizes the importance of adequate sampling and the simultaneous use of immunochemistry and/or flow cytometry to confirm the presence of more than a single type of lymphoma, which may be easily overlooked on microscopy alone.

Chemotherapy related changes in cfDNA levels in squamous non-small cell lung cancer: correlation with symptom scores and radiological responses.

Aim: There is limited data on prognostic value of baseline plasma cell free DNA (cfDNA) in advanced squamous non-small cell lung cancer (sq-NSCLC). This prospective observational study aimed to assess change in plasma cfDNA levels in locally-advanced/metastatic sq-NSCLC with chemotherapy and its correlation with symptom-scores and radiological-responses. Methods: Chemotherapy-naive patients with stages-IIIB/IIIC/IV sq-NSCLC (n = 59), smokers with chronic obstructive pulmonary disease [COPD, COPD-controls (CC); n = 27] and healthy-controls (n = 25) were enrolled. Respiratory symptom burden (RSB) and total symptom burden (TSB) were calculated from mean visual-analog-scores (VAS) of dyspnoea, cough, chest pain, hemoptysis RSB, anorexia and fatigue (all six for TSB). cfDNA was isolated from peripheral blood. All patients received platinum-doublet chemotherapy. RSB/TSB/cfDNA assessment and contrast-enhanced computed tomography (CECT)-thorax scans were done at baseline and post-chemotherapy. Results: At baseline, 13/59 (22%) sq-NSCLC, 3/27 (11%) CC and none (0%) healthy-controls had detectable cfDNA. All three CC were heavy smokers with no evidence of malignancy and undetectable cfDNA levels on repeat testing. In sq-NSCLC group, majority were males (95%), current-smokers (88%), heavy-smokers (70%), had metastatic disease (59%) with median age of 65 years. Eastern Co-operative Oncology Group (ECOG) performance status (PS) was 0-1 (56%) and 2 (42%). Median RSB- and TSB-scores were 9 [interquartile range (IQR) = 5-14] and 16 (IQR = 9-23), respectively. Of the 59 patients, 54 received ≥ 1 cycle while 27 underwent post-C4 evaluation with detectable cfDNA levels in 18/27 (66.7%). No baseline characteristic correlated with cfDNA detectability. Median overall survival (OS) and progression-free survival (PFS) were 262 days and 167 days, respectively. ECOG PS ≥ 2, RSB-score > 9 and TSB-score > 16 were all associated with worse OS and PFS as was cfDNA detectability [median OS = 97 days vs. 298 days and median PFS = 97 days vs. 197 days; P = 0.025; hazard ratio (HR) = 2.17]. Conclusions: Baseline cfDNA detectability is independently associated with poor OS and PFS in patients with advanced sq-NSCLC on chemotherapy.

Bridging the gap: understanding contemporary autopsies in acute leukemia by comparing ante-mortem and post-mortem profiles.

This study investigates acute myeloid leukemia/lymphoblastic leukemia (AML/ALL) through a 14-year analysis (2009-2022) of 46 autopsied cases (age >12 years). B-ALL was the dominant subtype (34.8%). Liver and spleen were the common sites of active leukemia (63% cases). Symptoms like dyspnea and altered sensorium associated significantly with heart (p = .031) and brain leukostasis (p = .006). Measurable residual disease (MRD) negativity correlated with disease-free status outside the bone marrow, while MRD-positive cases displayed leukemic infiltrates. Infections were identified in 23 autopsied cases, notably linked to post-induction and post-transplant fatalities. Surprisingly, 18 of these 23 cases had unexpected infections mainly fungal (13 cases) with Aspergillus species as the most common. Diagnostic discrepancies were identified in 48% of cases. Malignant infiltration (46%) and infections (25%) were the leading causes of death. This research sheds light on leukemia in extra-medullary tissues, uncovers novel clinical-pathological associations, and highlights overlooked therapy side effects, offering insights for future case management.

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.

A novel indirect ELISA for serodiagnosis of mucormycosis using antigens from Rhizopus arrhizus.

BACKGROUND: Due to a delay in diagnosis by conventional techniques and high mortality, the development of a standardised and rapid non-culture-based technique is an unmet need in pulmonary, gastrointestinal, and disseminated forms of mucormycosis. Though limited studies have been conducted for molecular diagnosis, there are no established serologic tests for this highly fatal infection. OBJECTIVE: To develop and evaluate an indirect in-house enzyme-linked immunosorbent assay (ELISA) utilising antigens of Rhizopus arrhizus for detecting anti-Rhizopus antibodies (IgG and IgM) in sera of patients with mucormycosis. METHODS: We extracted both secretory and mycelial Rhizopus antigens using standardised protocols. Bradford assay was used for protein quantification. We then standardised an indirect ELISA using R. arrhizus mycelial and secretory antigens (10.0 µg/mL in bicarbonate buffer pH 9.2) for detecting anti-Rhizopus IgG and IgM antibodies in patient sera. We included patients with mucormycosis, other fungal infections, and healthy controls. Antibody index value (E-value) was calculated for each patient sample. RESULTS: Asparagine broth culture filtrate utilising 85% ammonium sulphate salt fractionation and mycelial homogenate grown in yeast extract peptone dextrose (YPD) broth precipitated with trichloroacetic acid (TCA) yielded a large amount of good-quality protein for the assay. We included 55 patients with mucormycosis (rhino-orbito-cerebral mucormycosis [ROCM, n = 39], pulmonary [n = 15], gastrointestinal [n = 1]), 24 with other fungal infections (probable aspergillosis [n = 14], candidiasis [n = 10]), and healthy controls (n = 16). The sensitivity of the antibody test for diagnosing mucormycosis ranged from 83.6-92.7% for IgG and 72.7-87.3% for IgM, with a specificity of 91.7-92.5% for IgG and 80-82.5% for IgM. The sera from patients with other fungal infections and healthy individuals did not show significant cross-reactivity. CONCLUSION: The detection of anti-Rhizopus IgG antibody performed significantly better in comparison to IgM-based ELISA for diagnosing both ROCM (sensitivity of 84.6% vs. 69.2%) and pulmonary cases (86.6% vs. 80.0%). More extensive studies are required to confirm our findings.

Acute liver failure caused by lymphocyte-depleted Hodgkin lymphoma in tuberculosis and HIV-infected patient.

The lymphocyte-depleted classic Hodgkin lymphoma (LDCHL), the rarest subtype of classic Hodgkin lymphoma (CHL), is usually diagnosed at an advanced stage (stage IV) and one that unusually involves the liver, causing a rapidly progressive clinical course. We describe a 40-year-old immunocompromised man presenting with a progressive non-cholestatic jaundice and intermittent fever. The abdominal ultrasonography revealed a nodular liver with coarse echotexture and periportal hypodensities. The thoracic and abdominal contrast-enhanced computed tomography revealed right cervical and paraaortic lymphadenopathy, hepatosplenomegaly, diffuse mural thickening of duodenal and jejunal loops, and bilateral lobulated kidneys. Subsequently, he succumbed to his illness secondary to refractory septic shock. On postmortem examination, he was diagnosed with classic Hodgkin lymphoma (lymphocyte-depleted type) involving paraaortic and mediastinal lymph nodes based on morphology and immunochemistry findings. The lymphomatous process involved the liver (causing multiacinar confluent hepatic necrosis) and spleen, both showing tuberculous foci. This autopsy case depicts an uncommon case of acute liver failure due to infiltration of the liver by LDCHL in an HIV-infected patient. The findings of angiotropism and angioinvasion establish the pathological mechanism of liver failure (hepatocellular necrosis) in such cases.

FDG PET/CT in the Diagnosis and After Sunitinib Follow-up of Synchronous Base of Tongue and Thyroid Metastases From Renal Cell Carcinoma.

ABSTRACT: Renal cell carcinoma (RCC) is a leading cause of mortality among genitourinary malignancies with limited therapeutic options. The hematogenous route, lymphatic spread, and direct invasion have been documented in RCC. Usually, metastases are regional lymph nodes, lungs, bone, liver, adrenal glands, contralateral kidney, and brain. Metastases to the rare sites such as skin, breast, head and neck were documented in the literature. In the present case, we describe the synchronous metastases to the base of the tongue and thyroid gland in RCC and the response to sunitinib therapy on 18F-FDG PET/CT.

68 Ga-FAPI PET/CT in an Interesting Case of Metastatic Pulmonary Meningioma.

ABSTRACT: Meningiomas are one of the major primary CNS tumors. Most meningiomas are benign, but rarely, these metastasize to distant organs, the lungs being the commonest site of metastasis. 18 F-FDG PET/CT has been used to evaluate metastatic pulmonary meningioma. However, 68 Ga-FAPI PET/CT has not yet been evaluated. The present case highlights the 68 Ga-FAPI uptake in metastatic pulmonary meningioma in a postoperated case of left tentorial meningioma presenting with lung masses. Image-guided biopsy from the lung mass was consistent with metastatic meningioma.

Diagnostic Yield and Safety of the 19-Gauge versus 22-Gauge Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration Needle in Subjects with Sarcoidosis (GUESS).

INTRODUCTION: Observational data suggest that the 19-gauge (G) needle for endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) offers a higher diagnostic yield than the 22-G needle in sarcoidosis. No randomized trial has compared the yield of the two needles. METHODS: We randomized consecutive subjects with suspected sarcoidosis and enlarged thoracic lymph nodes to undergo EBUS-TBNA with either the 19-G or the 22-G needle. We compared the study groups for diagnostic sensitivity (primary outcome) assessed by the yield of granulomas in subjects finally diagnosed with sarcoidosis. We also compared the sample adequacy, difficulty performing the needle puncture assessed on a visual analog scale (VAS), the subject's cough intensity on an operator-rated VAS, and procedure-related complications (secondary outcomes). RESULTS: We randomized 150 (mean age, 43.0 years; 55% women) subjects and diagnosed sarcoidosis in 116 subjects. The diagnostic sensitivity of the 19-G needle (45/60, 75.0%) was not higher (p = 0.52) than the 22-G needle (39/56, 69.6%). We obtained adequate aspirates in 90.0% and 85.7% of subjects in the respective groups (p = 0.48). The operators had greater difficulty puncturing lymph nodes with the 19-G needle (p = 0.03), while the operator-assessed cough intensity was similar in the groups (p = 0.41). Transient hypoxemia was the only complication encountered during EBUS-TBNA (two subjects in either group). CONCLUSION: We did not find the 19-G needle superior to the 22-G in diagnostic sensitivity, specimen adequacy, or safety of EBUS-TBNA in sarcoidosis. Puncturing the lymph nodes was more difficult with the 19-G needle.

Cancer associated fibroblasts modulate the cytotoxicity of anti-cancer drugs in breast cancer: An in vitro study.

BACKGROUND: Tumour microenvironment (TME) contributes to resistance to anti-cancer drugs through multiple mechanisms including secretion of pro-survival factors by cancer associated fibroblasts (CAFs). In this study, we determined the chemotherapy resistance producing potential of CAFs in molecular subtypes of breast cancer. METHODS: The CAFs were isolated from fresh lumpectomy/mastectomy specimens of different molecular subtypes of breast cancer. The CAFs were cultured and secretome was collected from each breast cancer subtype. Breast cancer cell lines MCF-7, SK-BR3, MDA-MB-231, and MDA-MB-468 were treated with different doses of tamoxifen, trastuzumab, cisplatin, and doxorubicin alone respectively and in combination with secretome of CAFs from respective subtypes. MTT assay was done to check cell death after drug treatment. Liquid chromatography-mass spectrometry (LCMS) analysis of CAF secretome was also done. RESULTS: MTT assay showed that anti-cancer drugs alone had growth inhibitory effect on the cancer cells however, presence of CAF secretome reduced the anti-cancer effect of the drugs. Resistant to drugs in the presence of secretome, was determined by increased cell viability i.e., MCF-7, 51.02% to 63.02%; SK-BR-3, 34.22% to 44.88%; MDA-MB-231, 52.59% to 78.63%; and MDA-MB-468, 48.92% to 55.08%. LCMS analysis of the secretome showed the differential abundance of CAFs secreted proteins across breast cancer subtypes. CONCLUSIONS: The treatment of breast cancer cell lines with anti-cancer drugs in combination with secretome isolated from molecular subtype specific CAFs, reduced the cytotoxic effect of the drugs. In addition, LCMS data also highlighted different composition of secreted proteins from different breast cancer associated fibroblasts. Thus, TME has heterogenous population of CAFs across the breast cancer subtypes and in vitro experiments highlight their contribution to chemotherapy resistance which needs further validation.

The conundrum of breast cancer mimics.

The BIRADS lexicon ensures a standard reporting terminology in breast imaging and serves as a means of smooth communication between the radiologist and the referring physician. BIRADS assessment categories 4 and 5 warrant a biopsy to rule out underlying malignancy. However, a substantial number of cases in these categories sometimes turn out to be benign on biopsy. These benign mimics encompass inflammatory, sclerosing, neoplastic and a few other miscellaneous conditions. Awareness of these various mimics of breast cancer can equip the radiologist to handle these apparent cases of radiologic-pathological (rad-path) discordance better, guide overall patient management, avoiding inadvertent excisional biopsies and help alleviate patient anxiety and confusion.

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.

Periprosthetic metastases in carcinoma of unknown primary: A rare association.

ABSTRACT: Septic or aseptic loosening may cause bone loss around artificial prosthesis leading to prosthesis failure. This occurrence due to metastatic infiltration of bone or surrounding soft tissues is rare but has been occasionally reported. We report a case of an elderly lady presenting with swelling and pain at the site of previous hemiarthroplasty performed for traumatic injury. On evaluation, she was found to have a lytic femur lesion with a large soft-tissue component around the prosthetic joint. Biopsy suggested a metastatic carcinoma of renal origin, but screening of kidneys did not reveal any primary lesion. She had additional skeletal metastatic lesions but no other primary site was detected either. She was given palliative radiotherapy and systemic therapy (sunitinib) based on the histologic diagnosis of renal cell origin but did not tolerate it. Thereafter, she is continuing on zoledronate every 4 weeks and best supportive management since 4 months from diagnosis.

Impact of Anti-nuclear Antibody Seropositivity on Clinicopathological Parameters, Treatment Response, and Survival in Lymphoma Patients.

PURPOSE: Lymphoproliferative disorders and autoimmune diseases both are interrelated. The high incidence of lymphoma in autoimmune diseases and frequent antinuclear antibody (ANA) positivity in lymphoma patients have been observed. But the impact of ANA positivity on various clinical parameters and responses to therapy has not been elucidated properly. METHODS: In the present study, 73 treatment-naive lymphoma patients were recruited prospectively and samples were collected at baseline and after completion of therapy for evaluation of ANA. Comparative analysis was performed for various parameters between ANA-positive and ANA-negative groups. RESULTS: The prevalence of ANA at baseline was 27% in lymphoma patients which further increased to 35% after chemotherapy. The ANA-positive group had a significantly higher mean age (58±14.7 vs 47±19.9; p=0.01), early stage (77% vs 38%; p=0.02,) and infrequent B-symptoms (25% vs 52%; p=0.03) as compared to ANA-negative group. No significant difference was observed in the response to therapy and survival (both event-free and overall survival). The most frequent ANA pattern was speckled (50%) at baseline, and homogenous (42%) after the therapy. CONCLUSION: ANA is more frequent in lymphoma and increases further after chemotherapy. Higher mean age, early stage, and infrequent B symptoms were found to be significantly more frequent in ANA-positive lymphoma patients; however, only limited evidence supports its role as a prognostic marker or response to therapy. A wider study with appropriate follow-up data and molecular assay could shed light on the immunobiology of ANA production and its more defined clinical utility in lymphoma.

68 Ga-Pentixafor PET/CT for in-vivo mapping of CXCR4 receptors as potential radiotheranostic targets in soft tissue and bone sarcoma: preliminary results.

OBJECTIVE: To evaluate the diagnostic utility of 68 Ga-Pentixafor PET/CT for in vivo imaging of CXCR4 receptors in soft tissue/bone sarcoma. METHODS: Ten (7M: 3F; mean age = 24.7 ± 14.2 years) consecutive patients with clinical and radiological evidence of bone/soft tissue sarcoma were recruited prospectively whole body 68 Ga-Pentixafor PET/CT imaging was performed at 60-min after tracer administration. After performing standard CT, PET acquisition from head to toe was done (3 min/bed position) in a caudocranial direction. PET/CT data was reconstructed and SUV max , SUV mean values, target-to-background ratio (TBR) and active tumor volume (cc) were computed for the tracer avid lesions. Histopathological and IHC analysis was performed on the surgically excised primary tumors. CXCR4 receptors' intensity was evaluated by visual scoring. RESULTS: The mean SUV max and SUV mean values in the primary tumors were 4.80 ±â€…1.0 (3.9-7.7) and 2.40 ±â€…0.60 (0.9-4.0). The mean TBR and tumor volume (cc) were 1.84 ±â€…1.3 and 312.2 ±â€…285. Diagnosis of osteosarcoma in 7, chondrosarcoma, leiomyosarcoma and synovial sarcoma in 1 patient each was confirmed on HP analysis. Distant metastatic lesions were seen in 3/10 patients. Nuclear CXCR4 receptors' positivity was seen in 5, cytoplasmic in 4 and both pattern seen in 1 patient. The mean CXCR4 receptors' intensity was found to be 7.6 ±â€…2. The highest SUV max value of 7.7 was observed in the patient having both cytoplasmic and nuclear CXCR4 expression. SUV max was found to be poorly correlated ( r  = 0.441) with CXCR4 expression. CONCLUSION: 68 Ga-Pentixafor PET/CT detects CXCR4 receptors over-expressed in sarcoma, its radio-theranostics potential needs detailed evaluation.

Acute liver failure caused by lymphocyte-depleted Hodgkin lymphoma in tuberculosis and HIV-infected patient

ABSTRACT The lymphocyte-depleted classic Hodgkin lymphoma (LDCHL), the rarest subtype of classic Hodgkin lymphoma (CHL), is usually diagnosed at an advanced stage (stage IV) and one that unusually involves the liver, causing a rapidly progressive clinical course. We describe a 40-year-old immunocompromised man presenting with a progressive non-cholestatic jaundice and intermittent fever. The abdominal ultrasonography revealed a nodular liver with coarse echotexture and periportal hypodensities. The thoracic and abdominal contrast-enhanced computed tomography revealed right cervical and paraaortic lymphadenopathy, hepatosplenomegaly, diffuse mural thickening of duodenal and jejunal loops, and bilateral lobulated kidneys. Subsequently, he succumbed to his illness secondary to refractory septic shock. On postmortem examination, he was diagnosed with classic Hodgkin lymphoma (lymphocyte-depleted type) involving paraaortic and mediastinal lymph nodes based on morphology and immunochemistry findings. The lymphomatous process involved the liver (causing multiacinar confluent hepatic necrosis) and spleen, both showing tuberculous foci. This autopsy case depicts an uncommon case of acute liver failure due to infiltration of the liver by LDCHL in an HIV-infected patient. The findings of angiotropism and angioinvasion establish the pathological mechanism of liver failure (hepatocellular necrosis) in such cases.